1832
Hodgkin, T.
On some morbid appearances of the absorbent glands and spleen
Veröffentlicht:1832, Medical Chirurgical Transaction, 17, 69-97.
1865
Wilks, S.
enlargement of the lmyphatic glands and spleen (or Hodgkin´s disease), with remarks
Veröffentlicht: 1865, Guy´s Hospital Report, 11, 56-67.
1946
Goodman, L. S.Wintrobe, M. M.Dameshek, W.Goodman, M. J.Gilman, A.McLennan, M. T.
Nitrogen mustard therapy. Use of methyl-bis(beta-chloroethyl)amine hydrochloride and
tris(beta-chloroethyl)amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia
and certain allied and miscellaneous disorders.
Veröffentlicht: 1946, Jama, 132, 126-132 .
1966
Lukes, R. J.Butler, J.Hicks, E. B.
[The prognosis of Hodgkin's disease according to the histologic type and the clinical
stage. Role of the reactions of the host]
1967
DeVita, V. T., Jr.Carbone, P. P.
Treatment of Hodgkin's disease
Veröffentlicht: 1967, Med Ann Dist Columbia, 36, 232-4 passim .
1970
Devita, V. T., Jr.Serpick, A. A.Carbone, P. P.
Combination chemotherapy in the treatment of advanced Hodgkin's disease
Veröffentlicht: 1970, Ann Intern Med, 73, 881-95.
1971
Carbone, P. P.Kaplan, H. S.Musshoff, K.Smithers, D. W.Tubiana, M.
Report of the Committee on Hodgkin's Disease Staging Classification
1975
Bonadonna, G.Zucali, R.Monfardini, S.De Lena, M.Uslenghi, C.
Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP
| Veröffentlicht: |
1975, Cancer, 36, 252-9 |
| PubMedLink: |
|
| Abstract: | This paper reports the preliminary results of a controlled study randomizing MOPP vs. a new four-drug combination (ABVD) in advanced Hodgkin's disease. ABVD consists of 6 cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide. The purpose for designing this new combination was two-fold: to compare the efficacy of ABVD with MOPP, and to demonstrate absence of cross-resistance between the two regimens. Of 60 patients entered into the study, 45 (MOPP25, ABVD20) are presently evaluable for the analysis of remission induction. No patient was previously treated with chemotherapy; 20% had relapsed after primary radiotherapy. Whenever possible, complete remission was defined also through rebiopsy of known organ involvement. Complete remission occurred in 76% of patients treated with MOPP and in 75% of those given ABVD, with no difference between the two regimens as far as stage (IIIB-IIIS and IV), histologic type, and prior irradiation were concerned. Crossover carried out for progressive disease or for relapse after initial remission showed absence of cross-resistance between MOPP and ABVD. Toxic manifestations after ABVD were in general well tolerated and reversible. The percent of optimal dose for each drug was as follows: adriamycin 87%, vinblastine 87%, bleomycin 96%, and imidazole carboxamide 96%. These preliminary results indicate that in terms of complete remission, ABVD could represent a successful alternative to MOPP to be used either in MOPP failures or in sequential combination with MOPP. However, the lack of long-term followup limits at the present time an adequate comparison between the two treatments. |
Morgenfeld, M. C.Pavlovsky, A.Suarez, A.Somoza, N.Pavlovsky, S.Palau, M.Barros, C. A.
Combined cyclophosphamide vincristine, procarbazine, and prednisone (COPP) therapy of malignant lymphoma. Evaluation of 190 patients
| Veröffentlicht: |
1975, Cancer, 36, 1241-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1100220 |
| Abstract: |
One hundred ninety patients who had advanced active Hodgkin's disease, lymphosarcoma, or reticulum cell sarcoma were treated with a combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) given in a cyclical fashion every month. Complete remission was produced in 91 of 138 (66%) patients with Hodgkin's disease and in 39 of 52 (75%) patients with non-Hodgkin's lymphoma (lymphosarcoma and reticulum cell sarcoma). The response rate was higher in patients who completed six cycles of therapy compared to those who completed only three to five cycles: 77% vs. 45%, respectively, in Hodgkin's disease, and 85% vs. 46%, respectively, in non-Hodgkin's lymphoma. The median duration of remission was longer for Hodgkin's disease patients who completed six cycles (30 months vs. 10 months). The median duration of complete remission of non-Hodgkin's lymphoma was 14 months. The response to treatment correlated positively with survival. The median survival time start of COPP treatment for patients with Hodgkin's disease was 7 months for nonresponders, 14 months for those who attained partial remission, and more than 48 months for those who attained complete remission. For patients with non-Hodgkin's lymphoma, the median survival time from start of COPP treatment was 24 months for nonresponders and those who had partial remission, and more than 32 months for those who attained complete remission. Of complete remission responders with Hodgkin's disease, 70% are still alive 84 months after diagnosis, and 63% of the patients witn non-Hodgkin's lymphoma are still alive 48 months after diagnosis. |
1979
Fisher, R. I.DeVita, V. T.Hubbard, S. P.Simon, R.Young, R. C.
Prolonged disease-free survival in Hodgkin's disease with MOPP reinduction after first relapse
| Veröffentlicht: |
1979, Ann Intern Med, 90, 761-3 |
| PubMedLink: |
|
| Abstract: |
Thirty-two patients with Hodgkin's disease who relapsed after a first complete remission induced by nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) were retreated with MOPP chemotherapy. Nineteen patients achieved a second complete remission. Median duration of the second complete remission was 21 months. The likelihood of achieving a second complete response could be predicted by the duration of the first response. Fourteen of 15 patients whose first complete remission was longer than 12 months achieved a second complete response in contrast to five of 17 patients whose initial complete remission lasted less than 12 months (P less than 0.001). Median survival of all patients in this study who were re-treated with MOPP was longer than 4 years after their first relapse. We conclude that patients with Hodgkin's disease who relapse after a first complete remission induced by MOPP are not necessarily resistant to further MOPP therapy and can achieve long-term survival with MOPP reinduction. |
Santoro, A.Bonadonna, G.
Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)
| Veröffentlicht: |
1979, , 2, 101-5 |
| PubMedLink: |
|
| Abstract: |
Twenty-one patients with advanced Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, prednisone) were treated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). ABVD induced complete remission in 13 patients (62%) and partial remission in 2 (9.5%). In particular, complete response to ABVD was obtained in 7 of 13 patients who failed to respond to primary MOPP chemotherapy. After six cycles, no further therapy was given to patients in complete remission. At 36 months from starting ABVD, 69.7% of complete responders remain alive and free of disease, with a total survival of 73.4%. In contrast, none of the patients in whom partial response or nonresponse was observed was alive at 18 months. ABVD for six cycles was accompanied by mild and reversible toxicity. The results indicate that there is no cross-resistance between MOPP and ABVD. ABVD appears a simple effective, and tolerable multiple-drug chemotherapy for use in patients who are resistant to MOPP. |
1982
Goldie, J. H.Coldman, A. J.Gudauskas, G. A.
Rationale for the use of alternating non-cross-resistant chemotherapy
Veröffentlicht: 1982, Cancer Treat Rep, 66, 439-49
1983
Jones, S. E.Haut, A.Weick, J. K.Wilson, H. E.Grozea, P.Fabian, C. J.McKelvey, E.Byrne, G. E., Jr.Hartsock, R.Dixon, D. O.Coltman, C. A., Jr.
Comparison of adriamycin-containing chemotherapy (MOP-BAP) with MOPP-Bleomycin in the management of advanced Hodgkin's disease. A Southwest Oncology Group Study
| Veröffentlicht: |
1983, Cancer, 51, 1339-47 |
Miettinen, M.Franssila, K. O.Saxen, E.
Hodgkin's disease, lymphocytic predominance nodular. Increased risk for subsequent non-Hodgkin's lymphomas
| Veröffentlicht: |
1983, Cancer, 51, 2293-300 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6850508 |
| Abstract: |
Fifty-one cases of Hodgkin's disease, of lymphocytic predominance type, nodular subtype (HDLPN) were singled out from three sources: lymph nodes originally diagnosed as malignant lymphoma, nodes suspected of lymphoma and nodes suspected of toxoplasmosis. Two thirds of the 51 patients were men, and the median age was 42 years. The disease was characteristically unilocular and cervical and axillary nodes were most often involved. Local recurrences were common (in 13 cases). Oncological treatment (irradiation, cytostatics, or both) was given to 20 patients, whereas 31 patients remained untreated as the original histological diagnosis was not malignant. Despite the lack of treatment, the prognosis was good. Relative actuarial survival for the whole material was 93% at five years and 80% at ten years. During follow-up, five patients developed a diffuse large-celled non-Hodgkin's lymphoma 4-11 years after the onset of HDLPN. The majority of the subsequent lymphomas cannot be therapy-induced as only one of these patients had previously been treated (irradiated). Transition to other types of Hodgkin's disease was observed only in two cases. It is concluded that HDLPN is a clinicopathological entity with a good prognosis, but that it may sometimes change into a more malignant lymphoma of the Hodgkin's or non-Hodgkin's type. |
1984
Burns, B. F.Colby, T. V.Dorfman, R. F.
Differential diagnostic features of nodular L & H Hodgkin's disease, including progressive transformation of germinal centers
| Veröffentlicht: |
1984, Am J Surg Pathol, 8, 253-61 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6369997 |
| Abstract: |
The histologic features in 171 cases of nodular lymphocyte-predominant (L&H) Hodgkin's disease are presented and the association with an abnormal form of follicular hyperplasia termed "progressively transformed germinal centers" (PTGC) by Lennert is discussed. PTGC may closely resemble the nodules of L&H Hodgkin's disease and in 18% of our cases the two processes coexisted in the same lymph node. In addition, two patients had lymph node biopsies showing PTGC prior to biopsies showing nodular L&H Hodgkin's disease and three patients with histologically proved Hodgkin's disease were found to have PTGC in subsequent lymph node biopsies. Immunologic studies on frozen tissue sections from three cases of nodular L&H Hodgkin's disease showed that the neoplastic nodules contained abundant dendritic reticulum cells and B-lymphocytes with scattered T-lymphocytes. These findings suggest that the association between PTGC and nodular L&H Hodgkin's disease is more than coincidental and that this form of Hodgkin's disease preferentially involves B-cell areas of the lymph node, in contrast to the T-zone distribution in other forms of this disorder. |
1985
Lenhard, R. E., Jr.Order, S. E.Spunberg, J. J.Asbell, S. O.Leibel, S. A.
Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease
| Veröffentlicht: |
1985, J Clin Oncol, 3, 1296-300 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4045523 |
| Abstract: |
Thirty-eight patients with advanced, progressive Hodgkin's disease who had relapsed from or who had not responded to treatment with at least two potentially curative combination chemotherapy regimens were entered into this phase 2 study. All patients received 131I antiferritin antibody administered intravenously (IV) at a dose of 30 mCi on day 0 and 20 mCi on day 5. Antibody was derived from rabbit, pig, and monkey species. Objective partial remission of measurable disease was recorded in 40% of patients. Symptomatic response was recorded in 77% of patients. Toxicity was restricted to bone marrow depression with thrombocytopenia greater than leukopenia. These responses are comparable to other reported phase 2 drugs in this patient population and subsequent trials of antibody free of radioactivity and antibody using a beta emitting isotope are being carried out to expand upon these results. |
Zittoun, R.Audebert, A.Hoerni, B.Bernadou, A.Krulik, M.Rojouan, J.Eghbali, H.Merle-Beral, H.Parlier, Y.Diebold, J.et al.,
Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease
| Veröffentlicht: |
1985, J Clin Oncol, 3, 207-14 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3838188 |
| Abstract: |
From 1976 to 1981, 335 patients with untreated Hodgkin's disease, clinical stages I, II, and IIIA, have been treated by MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy, three to six cycles according to the prognostic factors, combined with radiotherapy. Irradiation was always performed after the first three cycles of chemotherapy, and was randomized between extensive radiotherapy, ie, mantle and paraaortic areas for supradiaphragmatic presentations, and radiotherapy restricted to the involved areas. No significant difference was observed between the two randomized branches for the disease-free survival (86% after six years in the involved field branch v 90% in the extended field branch), and none for the overall survival. Most of the relapses occurred in nonirradiated areas in the first group, and in irradiated areas in the second. Relapses were especially frequent in the IIE stages with pulmonary extension; extranodal relapses occurred with osseous and cutaneous localizations. Two cases of secondary leukemia were observed after three- or six-cycle MOPP plus radiotherapy limited to the involved areas. |
1986
Bonadonna, G.Valagussa, P.Santoro, A.
Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease. A report of 8-year results
| Veröffentlicht: |
1986, Ann Intern Med, 104, 739-46 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2422994 |
| Abstract: |
In patients with stage IV Hodgkin's disease mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) was randomly tested against MOPP alternated monthly with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). All 88 evaluable patients had not received chemotherapy and 25 had had a relapse after primary irradiation. The complete remission rate with MOPP/ABVD was 88.9% (40 of 45 patients), and with MOPP, 74.4% (32 of 43 patients). The 8-year results show that MOPP/ABVD was superior to MOPP in terms of freedom from progression (64.6% compared to 35.9%; p less than 0.005), relapse-free survival (72.6% compared to 45.1%; p less than 0.01), total survival (83.9% compared to 63.9%; p less than 0.06), and survival of complete responders (94.8% compared to 77.1%; p = 0.04). The delivery of MOPP/ABVD was not associated with an increased incidence of major toxicity. The early sequential rotation of two equally effective and non-cross-resistant drug combinations can substantially improve the likelihood of cure in patients with Hodgkin's disease. |
Hansmann, M. L.Wacker, H. H.Radzun, H. J.
Paragranuloma is a variant of Hodgkin's disease with predominance of B-cells
| Veröffentlicht: |
1986, Virchows Arch A Pathol Anat Histopathol, 409, 171-81 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3087053 |
| Abstract: |
Fifteen cases of Hodgkin's disease of nodular and diffuse paragranuloma subtype (nodular and diffuse subtype of lymphocyte predominant type of Hodgkin's disease) were studied by light and electron microscopy, using monoclonal antibodies recognizing T and B-lymphocytes and dendritic reticulum cells. The results were compared with findings on 10 cases of Hodgkin's disease of mixed type with lymphocyte predominance. The present study provides evidence that paragranuloma represents a special variant of Hodgkin's disease different from other subtypes. Paragranuloma is characterized by predominance of B-cells which were demonstrated with a new B cell reagent KiB3 on routinely processed paraffin sections. |
Longo, D. L.Young, R. C.Wesley, M.Hubbard, S. M.Duffey, P. L.Jaffe, E. S.DeVita, V. T., Jr.
Twenty years of MOPP therapy for Hodgkin's disease
| Veröffentlicht: |
1986, J Clin Oncol, 4, 1295-306 |
| PubMedLink: |
|
| Abstract: |
The results of treatment of 198 patients with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) for Hodgkin's disease were analyzed after a median of 14 years of follow-up. Throughout the period of follow-up, 103 patients have remained continuously free of disease. Review of biopsy specimens of 43 patients originally classified as Hodgkin's disease, lymphocyte-depleted type, revealed that ten of these patients actually had diffuse immunoblastic or large cell non-Hodgkin's lymphomas. Of the 188 patients with Hodgkin's disease, 157 achieved a complete response (CR) (84%), and 66% of them (101 patients) have remained disease-free more than 10 years from the end of treatment. Absence of B symptoms and receiving higher doses of vincristine were factors associated with a higher CR rate and longer survival. Patients entering complete remission in five cycles or less had significantly longer remissions than those requiring six or more cycles. Forty-eight percent of the Hodgkin's disease patients have survived between 9 and 21 years (median, 14 years) from the end of treatment. Nineteen percent of the CRs have died of intercurrent illnesses, free of Hodgkin's disease. |
Santoro, A.Viviani, S.Villarreal, C. J.Bonfante, V.Delfino, A.Valagussa, P.Bonadonna, G.
Salvage chemotherapy in Hodgkin's disease irradiation failures: superiority of doxorubicin-containing regimens over MOPP
| Veröffentlicht: |
1986, Cancer Treat Rep, 70, 343-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2420444 |
| Abstract: |
One hundred and twenty-two consecutive patients with Hodgkin's disease who relapsed after primary curative irradiation were treated with either MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) or a doxorubicin-containing regimen (ADM-Reg). The main pretreatment characteristics were comparable in the two groups. Complete remission was achieved in 74.6% of patients treated with MOPP (44 of 59) and in 90.5% of those given ADM-Reg (57 of 63). No difference was observed in the incidence of complete remission with regard to the type of ADM-Reg utilized [MABOP (mechlorethamine, doxorubicin, bleomycin, vincristine, and prednisone), 92.9%; ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), 95.6%; and MOPP alternated with ABVD, 84.6%]. The superiority of ADM-Reg versus MOPP was also confirmed in the 7-year analysis of freedom from disease progression (73.2% vs 42.2%), relapse-free survival (81.2% vs 54.3%), and overall survival (80.5% vs 44.4%). Thrombocytopenia was less frequently observed with ADM-Reg (30%), particularly following ABVD (13%), compared to MOPP (73%). The lowest incidence of alopecia occurred in patients given MOPP (15%) or MOPP/ABVD (19%). Acute nonlymphoblastic leukemia was observed in patients treated with MOPP (five of 59) and MABOP (one of 14). The observed findings indicate that in patients failing to respond to primary radiotherapy, salvage regimens containing doxorubicin are more effective than MOPP. Furthermore, combinations devoid of procarbazine and alkylating agents (ABVD) or with less intensive administration of these drugs (MOPP/ABVD) were not associated with secondary leukemia. |
Stein, H.Hansmann, M. L.Lennert, K.Brandtzaeg, P.Gatter, K. C.Mason, D. Y.
Reed-Sternberg and Hodgkin cells in lymphocyte-predominant Hodgkin's disease of nodular subtype contain J chain
| Veröffentlicht: |
1986, Am J Clin Pathol, 86, 292-7 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3529924 |
| Abstract: |
To throw light on the question of whether B-cell-derived forms of Hodgkin's disease exist, more than 100 cases of Hodgkin's disease (including all four major histologic categories) were investigated for the presence of J chain and were also immunostained for epithelial membrane antigen and the granulocyte-associated antigen X hapten. Reed-Sternberg and Hodgkin cells (RS & H) expressed J chain in 22 cases, 8 of which also expressed epithelial membrane antigen (EMA). X hapten was found in 62 cases, but all of these were J chain negative. J chain-positive RS & H cells were restricted to cases of lymphocyte-predominant disease, while X hapten-positive tumor cells were found frequently in nodular sclerosis, mixed cellularity, and lymphocyte-depletion Hodgkin's disease, but only occasionally in cases of lymphocyte-predominant disease. These findings indicate that nodular lymphocyte-predominant Hodgkin's disease differs from the other subtypes of Hodgkin's disease and that the neoplastic cells are of B-lymphoid origin. |
Timens, W.Visser, L.Poppema, S.
Nodular lymphocyte predominance type of Hodgkin's disease is a germinal center lymphoma
| Veröffentlicht: |
1986, Lab Invest, 54, 457-61 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3083157 |
| Abstract: |
Nodular lymphocyte predominance type of Hodgkin's disease can be distinguished from other subtypes of Hodgkin's disease on morphological and clinical grounds. Immunohistological studies on frozen tissue sections of seven cases of nodular lymphocyte predominance type of Hodgkin's disease (NLPHD) show differences in B cell, T cell, as well as dendritic cell population. NLPHD is confined to follicles which contain predominantly small lymphocytes, usually over 50% B cells and large numbers of B2+, anti-C3b+, anti-DRC+, and Ig- dendritic cells. The IgM+, IgD+, Leu8- B lymphocytes are of polyclonal origin. The T lymphocytes in these follicles are reactive with Leu7 in addition to T11, Leu1, T3, Leu3, and WT1. Leu7 is a monoclonal antibody reactive with natural killer cells, but also with a subpopulation of Leu3+ lymphocytes present in normal germinal centers. The population with this phenotype, not found in other types of Hodgkin's disease, appears to be greatly increased (up to 30%) in NLPHD. The so-called L&H type Sternberg-Reed (S-R) cells of NLPHD are transformed B cells, reactive with anti-B cell monoclonal antibodies which in some cases express detectable amounts of membrane and/or cytoplasmic immunoglobulin. Also, L&H type Sternberg-Reed cells in all cases stained for Ki-1 and Tac, and in three cases for LeuM1. Taken together, the findings indicate that NLPHD represents a proliferation of germinal center cells. |
1987
Hagemeister, F. B.Tannir, N.McLaughlin, P.Salvador, P.Riggs, S.Velasquez, W. S.Cabanillas, F.
MIME chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) as treatment for recurrent Hodgkin's disease
| Veröffentlicht: |
1987, J Clin Oncol, 5, 556-61 |
| PubMedLink: |
|
| Abstract: |
Forty-seven patients with Hodgkin's disease in relapse were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide). All patients had previously received nitrogen mustard, vincristine, prednisone, procarbazine (MOPP) or similar regimens and doxorubicin-containing combinations, and many had received extensive irradiation. Complete remission (CR) occurred in 23%, and was influenced by presence of extranodal disease, hemoglobin, lactic dehydrogenase (LDH), and number of prior relapses. Median survival for all patients was 50 weeks, and was affected adversely by the presence of extranodal disease and the number of prior relapses. Toxicity was significant, including infections (23%), neutropenic fever (34%), and hemorrhagic cystitis (23%), but was related in part to the extent of prior therapy. These results with this novel chemotherapy program in heavily pretreated patients suggest that MIME should be studied in less extensively treated patients and considered as a part of treatment programs for patients with Hodgkin's disease in first relapse. |
Pfreundschuh, M. G.Schoppe, W. D.Fuchs, R.Pfluger, K. H.Loeffler, M.Diehl, V.
Lomustine, etoposide, vindesine, and dexamethasone (CEVD) in Hodgkin's lymphoma refractory to cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD): a multicenter trial of the German Hodgkin Study Group
| Veröffentlicht: |
1987, Cancer Treat Rep, 71, 1203-7 |
| PubMedLink: |
|
| Abstract: |
Thirty-two patients with advanced Hodgkin's lymphoma resistant to cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were treated with a salvage chemotherapy regimen consisting of lomustine, etoposide, vindesine, and dexamethasone (CEVD). Twenty-seven patients were treated because of primary resistance to COPP/ABVD, and five patients were treated in early relapse (less than 12 months) after COPP/ABVD-induced complete remission. Fourteen patients (44%) achieved complete remission, and four patients achieved partial remission, with an overall response rate of 56%. Two partial responders achieved complete remission after additional radiotherapy. Four of five patients in early relapse after COPP/ABVD achieved complete remission. Consolidation radiotherapy was given for only one complete responder. Median duration of complete remission is greater than 10 months, and median survival is greater than 26 months. The treatment was well-tolerated. The main side effects were leukopenia, thrombocytopenia, mild nausea/vomiting, and cushingoid side effects. CEVD is a very active and well-tolerated salvage chemotherapy regimen in patients with Hodgkin's disease resistant to or relapsing after COPP and ABVD. |
Santoro, A.Bonadonna, G.Valagussa, P.Zucali, R.Viviani, S.Villani, F.Pagnoni, A. M.Bonfante, V.Musumeci, R.Crippa, F.et al.,.
Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy
| Veröffentlicht: |
1987, J Clin Oncol, 5, 27-37 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2433409 |
| Abstract: |
In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkin's disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy. |
Trudel, M. A.Krikorian, J. G.Neiman, R. S.
Lymphocyte predominance Hodgkin's disease. A clinicopathologic reassessment
| Veröffentlicht: |
1987, Cancer, 59, 99-106 |
| PubMedLink: |
|
| Abstract: |
A clinicopathologic analysis of 35 cases of lymphocyte predominance Hodgkin's disease (LPHD) was performed, and the relationship between various histologic features and stage at presentation was examined. The series comprised 31 male and 4 female patients with a median age of 32 years. Twenty patients had Ann Arbor Stage I disease; 5, Stage II; 8, Stage III; and 2, Stage IV. Eight cases showed a multifocal epithelioid histiocytic reaction; six of these had advanced-stage (III or IV) disease (P = 0.003). Five cases contained relatively frequent atypical mononuclear cells; four of these were Stage III or IV (P = 0.017). A purely diffuse growth pattern was also associated with high stage (P = 0.031). Presence of nodularity correlated with low stage (P = 0.031). During follow-up (median, 4 years; range, 2.5 months-18 years) there was a high incidence of second neoplasms (2 large cell lymphomas, 3 non-hematologic malignancies). LPHD manifests greater diversity of stage at presentation than originally thought. A high content of epithelioid histiocytes, relatively frequent atypical mononuclear cells, and diffuse histology appear to define subsets associated with advanced-stage disease. The correlation of nodular growth pattern with low-stage disease is consistent with the distinctive behavior and derivation of nodular LPHD. |
1989
Hansmann, M. L.Stein, H.Fellbaum, C.Hui, P. K.Parwaresch, M. R.Lennert, K.
Nodular paragranuloma can transform into high-grade malignant lymphoma of B type
| Veröffentlicht: |
1989, Hum Pathol, 20, 1169-75 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2591946 |
| Abstract: |
A follow-up study of 537 cases of Hodgkin's disease, lymphocyte predominance type, nodular--designated as nodular paragranuloma (NP)--found simultaneous presence of (n = 11) or subsequent transition into (n = 3) a large cell lymphoma (LCL) in 14 cases. Morphologically, the LCLs were classified in ten cases as centroblastic lymphoma (malignant lymphoma, diffuse, large cell, non-cleaved cell), in three cases as immunoblastic lymphoma (malignant lymphoma, large cell, immunoblastic), and in one case as large cell anaplastic lymphoma. Eleven of the 14 LCLs were studied immunohistologically. Five cases showed a monotypic immunoglobulin (Ig) pattern, seven were positive to the monoclonal B-cell marker Ki-B3, and three showed both monotypic Ig and Ki-B3 positivity. With anti-Ig and Ki-B3, nine of the 11 LCLs could be classified as B-cell non-Hodgkin's lymphoma. Only one case of LCL exhibited the typical phenotype of Hodgkin cells, ie, positivity to anti-CD15 (3C4) and anti-CD30 (Ber-H2). A retrospective follow-up study of these secondary LCLs of B type revealed a longer survival time than that of primary B-type LCLs and other secondary LCLs. These findings indicate that B-type LCL is the most common outcome when NP progresses into a lesion of higher malignancy and provide further evidence of a close relationship of NP to the B-cell system. They also suggest that it would be clinically relevant to distinguish between cases of B-type LCLs secondary to NP and cases of LCLs without association with NP. This implies that signs of a preexisting NP should be looked for when a B-type LCL is diagnosed. |
Lister, T. A.Crowther, D.Sutcliffe, S. B.Glatstein, E.Canellos, G. P.Young, R. C.Rosenberg, S. A.Coltman, C. A.Tubiana, M.
Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting
| Veröffentlicht: |
1989, J Clin Oncol, 7, 1630-6 |
| PubMedLink: |
|
| Abstract: |
The Ann Arbor classification for describing the stage of Hodgkin's disease at initial presentation has formed the basis upon which treatment is selected and has allowed comparison of results achieved by different investigators for almost two decades. A meeting was convened to review the classification and modify it in the light of experience gained in its use and new techniques for evaluating disease. It was concluded that the structure of the classification be maintained. It was particularly recommended: (1) that computed tomography (CT) be included as a technique for evaluating intrathoracic and infradiaphragmatic lymph nodes; (2) that the criteria for clinical involvement of the spleen and liver be modified to include evidence of focal defects with two imaging techniques and that abnormalities of liver function be ignored; (3) that the suffix 'X' to designate bulky disease (greater than 10 cm maximum dimension) be introduced; and (4) that a new category of response to therapy, unconfirmed/uncertain complete remission (CR[u]), be introduced to accommodate the difficulty of persistent radiological abnormalities of uncertain significance. |
Poppema, S.
The nature of the lymphocytes surrounding Reed-Sternberg cells in nodular lymphocyte predominance and in other types of Hodgkin's disease
| Veröffentlicht: |
1989, Am J Pathol, 135, 351-7 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2675617 |
| Abstract: |
The lymphocytes surrounding Reed-Sternberg cells may play an important role in the pathogenesis of Hodgkin's disease. In this study, T cells in different subtypes of Hodgkin's disease were analyzed in situ by an immunoperoxidase method employing a panel of antibodies, including several paraffin tissue-reactive monoclonal antibodies. The T cells in Hodgkin's disease-involved tissues were found to be activated CD4-positive T cells that are UCHL1+ and CD45R-. This immunophenotype is compatible with an activated helper-inducer memory T cell population. The T cells in the nodular lymphocyte predominance subtype were found to have additional positivity for Leu 7, indicating a subpopulation of CD4+ T cells, normally confined to the light zone of germinal centers of secondary follicles. |
1990
Engert, A.Burrows, F.Jung, W.Tazzari, P. L.Stein, H.Pfreundschuh, M.Diehl, V.Thorpe, P.
Evaluation of ricin A chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin's disease
| Veröffentlicht: |
1990, Cancer Res, 50, 84-8 |
| PubMedLink: |
|
| Abstract: |
Five monoclonal CD30 antibodies and two Fab' fragments were linked to deglycosylated ricin A chain (dgA), and their potential as immunotoxins for the treatment of Hodgkin's disease was evaluated. Cross-blocking experiments demonstrated that HRS-1, HRS-3, HRS-4, and Ber-H2 recognize the same epitope on the CD30 antigen and that Ki-1 binds to a different epitope. Scatchard analyses showed that HRS-3, HRS-4, and Ber-H2 bound strongly to L540 Hodgkin cells (Kd 15, 7, and 14 nM, respectively), whereas HRS-1 and Ki-1 bound more weakly (Kd 160 and 380 nM, respectively). The different affinities of the antibodies correlated closely with their cytotoxic potency as immunotoxins. HRS-3.dgA, HRS-4.dgA, and Ber-H2.dgA inhibited the protein synthesis of L540 cells by 50% at concentrations of 0.9-2.0 x 10(-10) M, whereas HRS-1.dgA and Ki-1.dgA were about 100 times less potent with 50% inhibitory concentrations of 0.8-1.0 x 10(-8) M. The most effective immunotoxins, HRS-3.dgA and HRS-4.dgA, were only 15 times less toxic than ricin itself. HRS-3 Fab'.dgA and HRS-4 Fab'.dgA were 7.8 and 3 times less potent than their IgG.dgA counterparts with 50% inhibitory concentrations of 7 x 10(-10) and 3 x 10(-10) M, respectively. Staining of human tissues revealed an unexpected cross-reactivity of HRS-4 with pancreatic cells of malignant and nonmalignant origin. HRS-1, HRS-3, Ber-H2, and Ki-1 showed very little cross-reactivity with any normal human tissues. It is concluded that HRS-3.dgA and HRS-3 Fab'.dgA are the immunotoxins of choice for in vivo therapy. |
Nicholas, D. S.Harris, S.Wright, D. H.
Lymphocyte predominance Hodgkin's disease--an immunohistochemical study
| Veröffentlicht: |
1990, Histopathology, 16, 157-65 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2323737 |
| Abstract: |
Lymph node biopsies from 57 local and referred cases, previously diagnosed at Southampton between 1978 and 1987 as lymphocyte predominance Hodgkin's disease were examined using the monoclonal antibodies MT1, UCHL1, L26, LN-1, E29/68 (EMA), Leu-M1 (CD15) and Ber-H2 (CD30). Of the 34 cases with a nodular architecture, 21 (19 male, two female) contained polylobated Reed-Sternberg cell variants with a B-cell phenotype, which lacked expression of CD15. In all cases, the polylobated cells showed positive staining with L26 and LN-1. Six cases expressed EMA and three showed positive staining with Ber-H2. Two cases lacking polylobated cells were reclassified as reactive follicular hyperplasia with progressive transformation of germinal centres. The remaining 11 cases had an atypical immunophenotype and were reclassified, mainly as mixed cellularity Hodgkin's disease. In six cases, the lymph node architecture showed a mixture of nodular and diffuse growth patterns. Five of these cases contained polylobated cells with the typical morphology and immunophenotype of those seen in nodular lymphocyte predominance Hodgkin's disease. The sixth case contained cells expressing CD15, and was reclassified as nodular sclerosing Hodgkin's disease. Of the fifteen biopsies with a diffuse architecture, four contained polylobated B-cells lacking expression of CD15. These were considered to be diffuse lymphocyte predominance Hodgkin's disease. The remaining 11 cases were reclassified as either Hodgkin's disease, mixed cellularity or as T-cell lymphomas. |
Roach, M., 3rdBrophy, N.Cox, R.Varghese, A.Hoppe, R. T.
Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease
| Veröffentlicht: |
1990, J Clin Oncol, 8, 623-9 |
| PubMedLink: |
|
| Abstract: |
Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value. |
1991
Armitage, J. O.Bierman, P. J.Vose, J. M.Anderson, J. R.Weisenburger, D. D.Kessinger, A.Reed, E. C.Vaughan, W. P.Coccia, P. F.Purtilo, D. T.
Autologous bone marrow transplantation for patients with relapsed Hodgkin's disease
| Veröffentlicht: |
1991, Am J Med, 91, 605-11 |
| PubMedLink: |
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1750430 |
| Abstract: |
PURPOSE: High-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkin's disease. Because patients with relapsed Hodgkin's disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkin's disease. PATIENTS AND METHODS: We treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT. RESULTS: The results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04). CONCLUSION: ABMT is a more effective therapy when used early for patients with relapsed Hodgkin's disease. |
Bennett, M. H.MacLennan, K. A.Vaughan Hudson, G.Vaughan Hudson, B.
Non-Hodgkin's lymphoma arising in patients treated for Hodgkin's disease in the BNLI: a 20-year experience. British National Lymphoma Investigation
| Veröffentlicht: |
1991, Ann Oncol, 2 Suppl 2, 83-92 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2049324 |
| Abstract: |
Twenty-two of 3033 patients with Hodgkin's disease (HD) randomised into the clinical trials of the BNLI have developed non-Hodgkin's lymphomas (NHLs) at periods up to 16 years after presentation (1 simultaneous and 1 composite), giving an incidence of 0.7%. The frequency of NHL varied from 3.8% in lymphocyte-predominant HD to 0.3% in nodular sclerosing HD. In this series, 16 patients developed high-grade NHL (12 B cell; 4 peripheral T cell) and 6 developed low-grade NHL (all B cell). The histological subtype of NHL did not appear to be related to initial histological subtype of HD or the treatment received. In histological subtypes other than lymphocyte predominant, there was commonly evidence of immunosuppression in the form of low presentation lymphocyte counts, advanced stage and systemic (B) symptoms. The results suggest that these patients have a propensity for lymphoproliferative disorders, possibly associated with some immune deficiency and the subsequent development of NHL is not treatment related. The findings also emphasise how important it is to biopsy recurrent disease. |
Cosset, J. M.Henry-Amar, M.Meerwaldt, J. H.
Long-term toxicity of early stages of Hodgkin's disease therapy: the EORTC experience. EORTC Lymphoma Cooperative Group
Jones, R. J.Ambinder, R. F.Piantadosi, S.Santos, G. W.
Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation
| Veröffentlicht: |
1991, Blood, 77, 649-53 |
| PubMedLink: |
|
| Abstract: |
The existence of an immunologic antileukemia reaction associated with allogeneic bone marrow transplantation (BMT) is well established. However, a similar graft-versus-tumor effect against lymphomas has not been demonstrated. We analyzed the results of BMT in 118 consecutive patients with relapsed Hodgkin's disease or aggressive non-Hodgkin's lymphoma. The 38 patients less than 50 years of age with HLA-matched donors had allogenic marrow transplants, and the other 80 patients received purged autologous grafts. The median age was 26 years in both the allogeneic and the autologous graft recipients. The patient's response to conventional salvage therapy before transplant was the only factor that influenced the event-free survival after BMT (P less than .001). Both the patient's response to salvage therapy before BMT (P less than .001) and the type of graft (P = .02) significantly influenced the probability of relapse after BMT. The actuarial probability of relapse in patients who responded to conventional salvage therapy before BMT was only 18% after allogenic BMT compared with 46% after autologous BMT. However, the actuarial probability of event-free survival at 4 years was the same, 47% versus 41%, for patients with responsive lymphomas who received allogeneic and autologous transplants, respectively (P = .8). The beneficial antitumor effect of allogeneic BMT was offset by its higher transplant-related mortality (P = .01), largely resulting from graft-versus-host disease. Allogeneic BMT appears to induce a clinically significant graft-versus-lymphoma effect. The magnitude of this effect is similar to that reported against leukemias. |
Vriesendorp, H. M.Herpst, J. M.Germack, M. A.Klein, J. L.Leichner, P. K.Loudenslager, D. M.Order, S. E.
Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin's disease, including Radiation Therapy Oncology Group 87-01
| Veröffentlicht: |
1991, J Clin Oncol, 9, 918-28 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2033428 |
| Abstract: |
Radiolabeled antiferritin immunoglobulin (Ig) preparations were tested in patients with advanced, end-stage Hodgkin's disease. Four patients received indium-111 (111In)-labeled monoclonal antiferritin (QCI). Targeting was not observed in tumor-bearing areas. Instead, scans showed rapid accumulation of QCI in normal liver. Forty-five patients were injected with 111In-labeled polyclonal antiferritin (rabbit, pig, or baboon). Forty (89%) patients showed tumor uptake, with dosimetric estimates ranging from 300 to 3,000 cGy in 1 week for the subsequently administered yttrium-90 (90Y)-labeled antiferritin. Yttrium-labeled antibody caused hematologic toxicity. Treatment-induced toxicity was not observed in any other organ system. Intravenous autologous bone marrow cells, 18 days after the yttrium infusion, accelerated hematopoietic recovery in eight patients receiving 30 mCi or 40 mCi. Hematopoietic recovery after a 20 mCi 90Y-labeled antiferritin infusion was not influenced by an autologous bone marrow transplant. Two patients receiving 20 mCi and one patient receiving 50 mCi remained aplastic after transplantation for unknown reasons. In 29 assessable patients, a 62% response rate was observed; nine of the 18 responses were complete. Responses ranging from 2 to 26 months were more commonly noted in patients with small tumors and long disease histories. Dosimetric calculations did not predict for responses. Recurrences frequently occurred in new areas instead of areas exhibiting bulky disease at the start of the treatment. Complete responses after 90Y antiferritin were significantly (P less than .02) more frequent than in a previous study with iodine-131 (131I) antiferritin. Further improvements are needed to make this new treatment modality curative. |
1992
Brada, M.Eeles, R.Ashley, S.Nichols, J.Horwich, A.
Salvage radiotherapy in recurrent Hodgkin's disease
| Veröffentlicht: |
1992, Ann Oncol, 3, 131-5 |
| PubMedLink: |
|
| Abstract: |
Forty-four patients with Hodgkin's disease (HD) which relapsed after chemotherapy were treated with salvage radiotherapy (S-RT) with curative intent. Patients were aged 7 to 80 years (median 32 years) at the time of S-RT and the median follow-up from S-RT was 5 years (1-15). Nine patients had recurrent HD following first-line chemotherapy and thirty five patients had refractory HD. Salvage therapy consisted of radiotherapy alone in 25 and combined chemotherapy and radiotherapy in 19 patients. The overall CR rate of salvage therapy was 66%. The overall median survival of 44 patients was 4.6 years from S-RT with 46% 5 year and 40% 10 year survivals. Age (greater than 40 years) and progression free interval (less than or equal to 1 year) were adverse independent prognostic factors for survival on multivariate analysis. The 5 and 10 year progression free survivals were 38% and 23% respectively. Adverse independent prognostic factors for progression-free survival were extranodal site of recurrence and short progression free interval (less than or equal to 1 year). We conclude that radiotherapy with or without chemotherapy has a role in the salvage of patients failing chemotherapy, particularly in those with nodal disease and progression-free interval greater than 1 year. |
Canellos, G. P.Anderson, J. R.Propert, K. J.Nissen, N.Cooper, M. R.Henderson, E. S.Green, M. R.Gottlieb, A.Peterson, B. A.
Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD
| Veröffentlicht: |
1992, N Engl J Med, 327, 1478-84 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1383821 |
| Abstract: |
BACKGROUND AND METHODS. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) has been the standard treatment for Hodgkin's disease for almost 20 years. In a randomized, multicenter trial, we compared three regimens of primary systemic therapy for newly diagnosed advanced Hodgkin's disease in Stages IIIA2, IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for 12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse after radiation therapy were eligible. No additional radiation therapy was given. Patients who did not have a complete response or who had a relapse with either MOPP alone or ABVD alone were switched to the opposite regimen. RESULTS. Of 361 eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD, and 115 received ABVD alone. The patients were stratified according to age, stage, previous radiation, histologic features, and performance status. The overall response rate was 93 percent, with complete responses in 77 percent: 67 percent in the MOPP group, 82 percent in the ABVD group, and 83 percent in the MOPP-ABVD group (P = 0.006 for the comparison of MOPP with the other two regimens, both of which contained doxorubicin). The rates of failure-free survival at five years were 50 percent for MOPP, 61 percent for ABVD, and 65 percent for MOPP-ABVD. Age, stage (III vs. IV), and regimen influenced failure-free survival significantly. Overall survival at five years was 66 percent for MOPP, 73 percent for ABVD, and 75 percent for MOPP-ABVD (P = 0.28 for the comparison of MOPP with the doxorubicin regimens). MOPP had more severe toxic effects on bone marrow than ABVD and was associated with greater reductions in the prescribed dose. CONCLUSIONS. In this trial, ABVD therapy for 6 to 8 months was as effective as 12 months of MOPP alternating with ABVD, and both were superior to MOPP alone in the treatment of advanced Hodgkin's disease. ABVD was less myelotoxic than MOPP or ABVD alternating with MOPP. |
Delabie, J.Vandenberghe, E.Kennes, C.Verhoef, G.Foschini, M. P.Stul, M.Cassiman, J. J.De Wolf-Peeters, C.
Histiocyte-rich B-cell lymphoma. A distinct clinicopathologic entity possibly related to lymphocyte predominant Hodgkin's disease, paragranuloma subtype
| Veröffentlicht: |
1992, Am J Surg Pathol, 16, 37-48 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1728195 |
| Abstract: |
This study reports six non-Hodgkin's lymphoma cases that we called histiocyte-rich B-cell lymphoma (BCL) because of the prominent reactive histiocytic infiltrate obscuring the malignant B-cell population. The involved lymph nodes are characterized by a mixed nodular and diffuse infiltrate and occasionally feature prominent sinuses. The infiltrate is composed of reactive lymphocytes and numerous histiocytes obscuring a tumor population composed of variably sized scattered cells with irregular or multilobar vesicular nuclei. Immunostaining of paraffin sections for the B-cell marker recognized by L26 helps in the identification of these neoplastic cells. The clonal nature and further evidence of the B-cell lineage of this condition is shown by immunoglobulin gene rearrangements detected in three cases. The six cases of histiocyte-rich BCL are remarkably similar clinically: all presented with stage IVB disease with splenomegaly and follow an aggressive clinical course. Except for these features, our series show striking similarities to paragranuloma lymphocyte-predominant Hodgkin's disease, including male preponderance (all patients are male), age distribution (mean age, 41 years), propensity to progress to a diffuse, large B-cell lymphoma (two cases), as well as morphology of the neoplastic B-cell population and expression of Hodgkin's cell markers (Leu-M1 positivity after neuraminidase digestion in three cases, Leu-M1 positivity without neuraminidase digestion in one case, and additional epithelial membrane antigen [EMA] positivity in two cases). Both morphologically and clinically, the present series can be differentiated from other types of infiltrate-rich BCL, such as T-cell-rich BCL. Although additional cases will have to be recognized, histiocyte-rich B-cell lymphoma most likely represents a distinct clinicopathological entity. We speculate that it develops from a subset of B cells that also gives rise to the lymphocytic-histiocytic (L/H) cell, the Hodgkin's cell variant of lymphocyte-predominant Hodgkin's disease, paragranuloma subtype. |
Henry-Amar, M.
Second cancer after the treatment for Hodgkin's disease: a report from the International Database on Hodgkin's Disease
| Veröffentlicht: |
1992, Ann Oncol, 3 Suppl 4, 117-28 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1450072 |
| Abstract: |
Twenty institutions/cooperative groups tabulated second cancers among 12,411 patients diagnosed with Hodgkin's disease between 1960 and 1987, giving 82,850 person-years of observation. Overall, 631 second cancers were observed, as compared with 223.25 expected (observed (O) to expected (E) ratio 2.83, p < 0.001) at least one year after the diagnosis of Hodgkin's disease. Second cancers were acute leukaemias (AL) in 158 cases as compared with 5.75 expected (O/E = 27.48, p < 0.001), non-Hodgkin's lymphomas (NHL) in 106 cases as compared with 3.34 expected (O/E = 31.77, p < 0.001), and solid tumors (ST) in 367 cases as compared with 214.16 expected (O/E = 1.71, p < 0.001), with no differences between males and females. Excess of ST was observed for the following anatomic sites: salivary gland, small intestine, colon, bronchus, pleura, bone, skin other than melanoma and thyroid in males; salivary gland, bronchus, pleura, skin other than melanoma and breast in females. While the excess of second AL and NHL was significant over the 1-14 year period after the start of initial therapy, that of second ST became apparent after the fifth year, increasing with time. Overall, the 15-year cumulative incidence rate of second cancer was 11.2%. It was 2.2%, 1.8% and 7.5% for second AL, NHL and ST, respectively. While the cumulative incidence of AL and NHL plateaued after 17 years, that of ST was still increasing. To analyse whether a particular treatment category was associated with an increased risk of second cancer, a prognostic study was performed on the 11,241 patients who achieved a complete remission and were continuously disease-free. Overall, 87 patients developed an AL, 68 a NHL, and 231 a ST. Combined modality treatments including MOPP or MOPP-like chemotherapy were associated with the higher risk of second AL (Relative risk (RR) = 17.11; p < 0.001) followed by age above 50 (RR > 4.50; p < 0.001), advanced clinical stage (RR > 2.50; p < 0.001), splenectomy (RR = 1.65; p < 0.05) and MOPP or MOPP-like chemotherapy used alone (RR = 2.20; p < 0.05). Factors associated with an increased risk of second NHL were age above 30 (RR > 3.5; p < 0.001), male gender (RR = 1.82; p < 0.05) and clinical stage III (RR = 1.70; p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) |
Longo, D. L.Duffey, P. L.Young, R. C.Hubbard, S. M.Ihde, D. C.Glatstein, E.Phares, J. C.Jaffe, E. S.Urba, W. J.DeVita, V. T., Jr.
Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure
| Veröffentlicht: |
1992, J Clin Oncol, 10, 210-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1732422 |
| Abstract: |
PURPOSE: The study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission. PATIENTS AND METHODS: Study population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission. RESULTS: Half of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or longer than 1 year) made a significant impact on survival. Patients whose initial remission was longer than 1 year had significantly higher complete response rates to salvage therapy, significantly more durable second remissions, and significantly longer survival than patients whose initial remission was shorter than 1 year. Survival beyond 11 years from relapse of patients with long initial remissions was 24%; for those with short initial remissions, 11% (P2 = .027). Despite the fact that with salvage therapy, patients with long initial remission had an 85% complete response rate to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) with a disease-free survival of 45% at 20 years, acute leukemia and other treatment-related complications combined to lower the survival rate of this more favorable subset. CONCLUSIONS: These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support. |
1993
Anderson, J. E.Litzow, M. R.Appelbaum, F. R.Schoch, G.Fisher, L. D.Buckner, C. D.Petersen, F. B.Crawford, S. W.Press, O. W.Sanders, J. E.et al.,
Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience
| Veröffentlicht: |
1993, J Clin Oncol, 11, 2342-50 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. PATIENTS AND METHODS: Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. RESULTS: The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. CONCLUSION: Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow. |
Bierman, P. J.Bagin, R. G.Jagannath, S.Vose, J. M.Spitzer, G.Kessinger, A.Dicke, K. A.Armitage, J. O.
High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease: long-term follow-up in 128 patients
| Veröffentlicht: |
1993, Ann Oncol, 4, 767-73 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8280658 |
| Abstract: |
BACKGROUND: There is little long-term follow-up information after autologous transplantation for Hodgkin's disease. We evaluated the influence of various prognostic factors and examined the outcome in 128 such patients. PATIENTS AND METHODS: Patients received high dose cyclophosphamide, carmustine, and etoposide followed by autologous hematopoietic rescue. RESULTS: Patients have been observed between 50-130 months (median 77 months) following transplantation. Overall survival at four years is estimated as 45 percent, and failure-free survival as 25 percent. The best results were seen in patients with a good performance status, who had failed at most one prior chemotherapy regimen. Failure-free survival at four years is estimated as 53 percent for this group. Relapses more than 24 months after transplantation were seen in 11 patients. Five patients developed myelodysplastic syndromes. Three patients became pregnant after the transplant. CONCLUSIONS: Prolonged failure-free survival may be observed following high dose chemotherapy and autologous hematopoietic rescue in patients with Hodgkin's disease. Superior results were seen in patients without extensive prior chemotherapy and in those with a good performance status. Late relapses and deaths from secondary myelodysplastic syndromes mandate prolonged follow-up after autologous transplantation for Hodgkin's disease. |
Bierman, P. J.Vose, J. M.Leichner, P. K.Quadri, S. M.Armitage, J. O.Klein, J. L.Abrams, R. A.Dicke, K. A.Vriesendorp, H. M.
Yttrium 90-labeled antiferritin followed by high-dose chemotherapy and autologous bone marrow transplantation for poor-prognosis Hodgkin's disease
| Veröffentlicht: |
1993, J Clin Oncol, 11, 698-703 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8478663 |
| Abstract: |
PURPOSE: This study was undertaken to examine the feasibility of combining radiolabeled antibody therapy with high-dose chemotherapy followed by autologous bone marrow transplantation in patients with poor-prognosis Hodgkin's disease. PATIENTS AND METHODS: Patients were entered onto this protocol if they had chemotherapy-resistant disease, bulky disease, or extensive prior therapy. Patients received yttrium-labeled antiferritin on day -13, -12, or -11, followed by high-dose cyclophosphamide, carmustine, and etoposide (CBV) on days -6 to -3, and then bone marrow infusion on day 0. RESULTS: Twelve patients received both radiolabeled antibody and high-dose chemotherapy followed by autologous transplantation. Two additional patients started the study, but were unable to complete all therapy. Four of 12 patients experienced early transplant-related mortality. Four patients are alive more than 2 years following transplantation and three are free from disease progression at 24+, 25+, and 28+ months following transplantation. The progression-free survival rate at 1 year is estimated to be 21%. Considering the poor prognostic characteristics of these patients, toxicity on this protocol was not necessarily greater than that observed with high-dose chemotherapy alone. CONCLUSION: This report demonstrates the feasibility of combining radiolabeled antibody therapy with high-dose chemotherapy and autologous bone marrow transplantation. |
Carde, P.Hagenbeek, A.Hayat, M.Monconduit, M.Thomas, J.Burgers, M. J.Noordijk, E. M.Tanguy, A.Meerwaldt, J. H.Le Fur, R.et al.,
Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group
| Veröffentlicht: |
1993, J Clin Oncol, 11, 2258-72 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7693881 |
| Abstract: |
PURPOSE: To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS: The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS: In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION: Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation. |
Hancock, S. L.Tucker, M. A.Hoppe, R. T.
Factors affecting late mortality from heart disease after treatment of Hodgkin's disease
| Veröffentlicht: |
1993, Jama, 270, 1949-55 |
| PubMedLink: |
|
| Abstract: |
OBJECTIVE--To assess the risk of death from heart disease after Hodgkin's disease therapy. DESIGN--Retrospective study comparing treated patients with a matched general population. SETTING--Referral center. PATIENTS--A total of 2232 consecutive Hodgkin's disease patients treated from 1960 through 1991. Follow-up averaged 9.5 years. MAIN OUTCOME MEASURES--Relative risks (RRs), the ratio of the observed to the expected cases with 95% confidence intervals (CIs), chi tests for trends, and Kaplan-Meier actuarial risks. RESULTS--Of the 2232 patients, 88 (3.9%) died of heart disease, 55 from acute myocardial infarction and 33 from other cardiac diseases, including congestive heart failure, radiation pericarditis or pancarditis, cardiomyopathy, or valvular heart disease. The RR for cardiac death was 3.1 (CI, 2.4 to 3.7). Mediastinal radiation of 30 Gy or less (n = 385 patients) did not increase risk; above 30 Gy (n = 1830), RR was 3.5 (CI, 2.7 to 4.3). Blocking to limit cardiac exposure reduced the RR for other cardiac diseases from 5.3 (CI, 3.1 to 7.5) to 1.4 (CI, 0.6 to 2.9), but not acute myocardial infarction (RR, 3.7 vs 3.4). The RRs increased with duration after treatment (trend in acute myocardial infarction, P = .02; in other cardiac diseases, P = .004). The RR for acute myocardial infarction was highest after irradiation before 20 years of age and decreased with increasing age at treatment (P < .0001 for trend). CONCLUSIONS--Mediastinal irradiation for Hodgkin's disease increases the risk of subsequent death from heart disease. Risk increased with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increasing duration of follow-up. |
Kamel, O. W.Gelb, A. B.Shibuya, R. B.Warnke, R. A.
Leu 7 (CD57) reactivity distinguishes nodular lymphocyte predominance Hodgkin's disease from nodular sclerosing Hodgkin's disease, T-cell-rich B-cell lymphoma and follicular lymphoma
| Veröffentlicht: |
1993, Am J Pathol, 142, 541-6 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7679553 |
| Abstract: |
Several recent reports have suggested that nodular lymphocyte predominance Hodgkin's disease (NLPHD) may be distinct from other forms of Hodgkin's disease and may be more closely related to B-cell non-Hodgkin's lymphoma. This is primarily based on immunophenotypic studies that have shown that the L & H cells in NLPHD demonstrate a B-cell phenotype. In 1989, Poppema reported that the T cells in NLPHD differ from T cells in other forms of Hodgkin's disease in that they demonstrate reactivity for Leu 7 (CD57). In this study we tested the hypothesis that Leu 7 (CD57) reactivity of small lymphocytes in NLPHD is an immunophenotypic feature that distinguishes NLPHD from nodular sclerosing Hodgkin's disease and from certain B-cell lymphomas that may histologically simulate NLPHD, namely T-cell-rich B-cell lymphoma and follicular lymphoma. Using an image analysis method, we found Leu 7 (CD57) reactivity in an average of 18.9% of the small lymphocytes in the nodules of NLPHD compared with 3.9% in nodular sclerosing Hodgkin's disease, 4.3% in T-cell-rich B-cell lymphoma, and 2.1% in follicular lymphoma. Moreover, Leu 7 (CD57)-reactive small lymphocytes often showed a distinctive pattern in NLPHD, forming a ring of cells around the large L & H cells. While scattered Leu 7 (CD57)-reactive lymphocytes were found in the other disorders, the percentage of reactive cells and the pattern of reactivity were significantly different in NLPHD. These results suggest that Leu 7 (CD57) reactivity may be used as an additional immunophenotypic criterion in distinguishing NLPHD from nodular sclerosing Hodgkin's disease, T-cell-rich B-cell lymphoma, and follicular lymphoma. The clinical and biological significance of Leu 7 (CD57) reactivity of small lymphocytes in NLPHD merits further investigation. |
Linch, D. C.Winfield, D.Goldstone, A. H.Moir, D.Hancock, B.McMillan, A.Chopra, R.Milligan, D.Hudson, G. V.
Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial
| Veröffentlicht: |
1993, Lancet, 341, 1051-4 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8096958 |
| Abstract: |
High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation (ABMT) are increasingly used for the treatment of relapsed and resistant Hodgkin's disease, although there has been no randomised trial of this treatment. The British National Lymphoma Investigation therefore undertook a randomised comparison of high-dose chemotherapy (BEAM = carmustine, etoposide, cytarabine, and melphalan) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue (mini-BEAM) in patients with active Hodgkin's disease, for whom conventional therapy had failed. 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM. All have been followed up for at least 12 months (median 34 months). 5 BEAM recipients have died (2 from causes related to ABMT and 3 from disease progression) compared with 9 mini-BEAM recipients (all disease progression). This difference was not significant (p = 0.318). However, both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT (p = 0.025 and p = 0.005, respectively). Recruitment to the trial became increasingly difficult because patients refused randomisation and requested ABMT. It was therefore closed early (40 patients rather than 66 intended). Nevertheless, we found a dose-response effect in these patients with relapsed and resistant Hodgkin's disease. High doses facilitated by ABMT can lead to better disease-free survival. |
1994
Kuppers, R.Rajewsky, K.Zhao, M.Simons, G.Laumann, R.Fischer, R.Hansmann, M. L.
Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development
| Veröffentlicht: |
1994, Proc Natl Acad Sci U S A, 91, 10962-6 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7971992 |
| Abstract: |
Hodgkin disease (HD) is characterized by a small number of putative malignant cells [Hodgkin and Reed-Sternberg (HRS) cells] among a background of lymphocytes and histiocytes. The lineage of HRS cells is still elusive and a clonal origin of these rare cells has not formally been demonstrated. We isolated HRS cells by micromanipulation from histological sections of three cases of Hodgkin lymphoma (each representing a distinct subtype of the disease) and analyzed individual cells for immunoglobulin variable (V) gene rearrangements by PCR. In each of the three cases a single heavy-chain V (VH) (and in one case, in addition, a kappa light-chain) gene rearrangement was amplified from the HRS cells, identifying these cells as members of a single clone. A potentially functional VH rearrangement was obtained from a case of nodular sclerosis HD. Somatic mutations and intraclonal diversity in the VH genes indicate a germinal center B-cell origin of the HRS cells in a case of lymphocyte-predominant HD, whereas in a case of mixed-cellularity HD the sequence analysis revealed only nonfunctional V gene rearrangements, suggesting a pre-B-cell origin. This indicates that HRS cells can originate from B-lineage cells at various stages of development. |
Pfreundschuh, M. G.Rueffer, U.Lathan, B.Schmitz, N.Brosteanu, O.Hasenclever, D.Haas, R.Kirchner, H.Koch, P.Kuse, R.et al.,
Dexa-BEAM in patients with Hodgkin's disease refractory to multidrug chemotherapy regimens: a trial of the German Hodgkin's Disease Study Group
| Veröffentlicht: |
1994, J Clin Oncol, 12, 580-6 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: A prospective phase II study was conducted to evaluate the efficacy of dexamethasone, carmustine, etoposide, cytarabine, and melphalan (Dexa-BEAM) as salvage chemotherapy for patients with Hodgkin's disease. PATIENTS AND METHODS: Fifty-five patients progressing on or relapsing after eight- or 10-drug chemotherapy (cyclophosphamide, vincristine, procarbazine, and prednisone plus doxorubicin, bleomycin, vinblastine, and dacarbazine [COPP+ABVD] or COPP+ABV+ifosfamide, methotrexate, etoposide, and prednisone [IMEP]) were treated with Dexa-BEAM. Patients who responded after two cycles of Dexa-BEAM either continued treatment for another two to three cycles or received high-dose chemotherapy/autologous bone marrow transplantation (HDCT/ABMT) with cyclophosphamide, etoposide, and carmustine (BCNU) (CVB) as conditioning regimen. RESULTS: Seventeen patients (31%) achieved a complete remission and 16 (29%) a partial remission, resulting in a response rate of 60% (95% confidence interval, 46% to 73%). Progressive disease developed in 18 patients. Toxicity of Dexa-BEAM was acceptable with pronounced, but temporary World Health Organization (WHO) grade III/IV granulocytopenia and thrombocytopenia occurring in more than 90% of all courses. Two patients died of sepsis during granulocytopenia. Three prognostic subgroups could be distinguished: (1) patients progressing on initial chemotherapy, (2) patients relapsing within 12 months, and (3) patients with late relapses. The response rates for these groups were 52%, 60%, and 83%, and the median survival duration 12, 29, and 40+ months, respectively. In a nonrandomized comparison, the survival of patients who responded to two cycles of Dexa-BEAM and had additional cycles of Dexa-BEAM (n = 14) was not different from those responding patients who underwent HDCT/ABMT (n = 19). However, the power to detect a 20% survival difference was only 33% in this comparison. CONCLUSION: Dexa-BEAM is an effective salvage treatment for patients with Hodgkin's disease who fail to respond to multidrug chemotherapy. Efficacy and toxicity are comparable to HDCT/ABMT and underline the need for prospective randomized trials to define better the role of HDCT with and without ABMT in these patients. |
Reece, D. E.Connors, J. M.Spinelli, J. J.Barnett, M. J.Fairey, R. N.Klingemann, H. G.Nantel, S. H.O'Reilly, S.Shepherd, J. D.Sutherland, H. J.et al.,
Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy
| Veröffentlicht: |
1994, Blood, 83, 1193-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8118023 |
| Abstract: |
The optimal timing in which to use intensive chemotherapy and autologous bone marrow transplantation (BMT) in Hodgkin's disease (HD) is uncertain. In 1985, we initiated a program in which this modality was used as the initial salvage therapy in patients relapsing after combination chemotherapy. Fifty-eight patients with HD in first relapse after primary chemotherapy received conditioning with high-dose cyclophosphamide, carmustine, etoposide (VP16-213) +/- cisplatin (CBV +/- P) followed by autologous BMT. All but six of these patients were given a median of two cycles of conventional chemotherapy +/- involved field radiation therapy before CBV +/- P and autologous BMT. These measures were not used as a means for patients selection; all patients receiving such therapy ultimately were transplanted. The probability of nonrelapse mortality, progression of HD, and progression-free survival post-BMT were calculated, and prognostic factors for progression-free survival were evaluated using the Cox proportional hazards method. Treatment-related deaths occurred in only three patients. Thirteen patients have relapsed at a median 0.7 years (range 0.1 to 3.5) post-BMT. At a median follow-up of 2.3 years (range 0.4 to 7.2), the actuarial progression-free survival is 64% (95% confidence interval, 46% to 78%). In the statistical analysis, three similarly weighted but independent prognostic factors were identified: "B" symptoms at relapse, extranodal disease at relapse, and initial remission duration of less than 1 year. Patients with no risk factors had a 3-year progression-free survival of 100%, compared with 81% in patients with one factor, 40% in those with two factors, and 0% in patients with all three factors. CBV +/- P and autologous BMT is highly effective salvage therapy for HD patients in a first relapse, particularly in the subset of patients with less than two adverse factors. Therapy must be improved in the future for patients with > or = 2 adverse factors. |
Specht, L.Horwich, A.Ashley, S.
Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease
| Veröffentlicht: |
1994, Int J Radiat Oncol Biol Phys, 30, 805-11 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681 patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology, presentation (supra- vs. infradiaphragmatic), number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, lactate dehydrogenase, alkaline phosphatase, serum albumin, and hemoglobin. RESULTS: Only age and histology showed significant prognostic impact in univariate and multivariate analyses. The influence of age may perhaps be attributed to suboptimal treatment of some older patients. Patients with nodal relapse had a better prognosis than patients with extranodal relapse, probably indicating that the latter had more extensive disease at relapse. The length of the initial disease-free interval had no influence on prognosis after relapse. CONCLUSION: The decisive factors for outcome after initial treatment with irradiation alone are a) the factors predicting the risk of relapse after initial radiotherapy and b) the factors predicting outcome after relapse, that is, histologic subtype and extent of disease at relapse. |
1995
Alkan, S.Ross, C. W.Hanson, C. A.Schnitzer, B.
Epstein-Barr virus and bcl-2 protein overexpression are not detected in the neoplastic cells of nodular lymphocyte predominance Hodgkin's disease
| Veröffentlicht: |
1995, Mod Pathol, 8, 544-7 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7675775 |
| Abstract: |
Recent studies have indicated that nodular lymphocyte predominance Hodgkin's disease (nLP-HD) is a B-cell lymphoma. Although molecular events in the neoplastic transformation of B-cells are not well understood, Epstein-Barr virus infection and bcl-2 protein overexpression have been postulated to have etiologic roles in some lymphomas. Epstein-Barr virus has been demonstrated in the Reed-Sternberg cells of Hodgkin's disease cases (other than nLP-HD) as well as in some B-cell lymphomas; bcl-2 overexpression is found in the majority of follicular lymphomas. The biologic role for bcl-2 in HD is controversial. Some reports have indicated the presence of bcl-2 gene rearrangements, associated with the t(14;18) (q32;q21), detected by the polymerase chain reaction in HD; recent studies have failed to confirm this finding. Reports in the literature describe only a few such analyses in the nLP-HD subtype. To address these conflicting issues, we examined 12 cases of nLP-HD to determine whether bcl-2 protein expression (by immunohistochemistry) and Epstein-Barr virus (by in situ hybridization) could be detected in the Reed-Sternberg variants. None of the cases showed expression of bcl-2 protein or Epstein-Barr virus RNA in the neoplastic cells. Epstein-Barr virus does not appear to play an important role in the pathogenesis of nLP-HD. Similarly, we cannot substantiate a role for bcl-2 in the development of this type of Hodgkin's disease. |
Bartlett, N. L.Rosenberg, S. A.Hoppe, R. T.Hancock, S. L.Horning, S. J.
Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report
| Veröffentlicht: |
1995, J Clin Oncol, 13, 1080-8 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: Although survival rates have improved for patients with bulky and advanced-stage Hodgkin's disease (HD), current treatments entail substantial acute morbidity and risks for late effects such as infertility, second malignancies, and cardiopulmonary toxicities. A novel, brief chemotherapy regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, doxorubicin, and bleomycin, and maintain dose-intensity (DI). This brief chemotherapy was combined with radiation therapy (RT) to bulky disease sites. METHODS: Since May 1989, 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement (n = 21) or for stage III or IV HD (n = 44). Patients received weekly chemotherapy for 12 weeks. Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy; in the remaining 40 patients, RT was limited to bulky disease (adenopathy > or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]). RESULTS: With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II patients with bulky mediastinal disease and 82% for patients with stage III to IV disease. There were no treatment-related deaths. In a preliminary analysis on a subset of patients, female and male fertility appears to be preserved. CONCLUSION: These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage HD. Less cumulative exposure to alkylating agents, doxorubicin, and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity. Based on these results, the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a randomized clinical trial. |
Carbone, A.Gloghini, A.Gattei, V.Aldinucci, D.Degan, M.De Paoli, P.Zagonel, V.Pinto, A.
Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines
| Veröffentlicht: |
1995, Blood, 85, 780-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7530508 |
| Abstract: |
CD40 is a member of the nerve growth factor receptor family, showing a significant homology to the Hodgkin's disease (HD)-associated antigen CD30 and is capable of transduce growth signals in a number of cell types. A series of 312 lymphoma samples, including 139 cases of HD, 32 cases of CD30+ anaplastic large cell (ALC) lymphomas, 141 cases of other non-Hodgkin's lymphomas (NHLs), and a panel of HD- or NHL-derived cell lines, were evaluated for CD40 expression by immunostaining of paraffin embedded sections, cell smears and flow cytometry. CD40 was strongly expressed with a highly distinct pattern of staining on Reed-Sternberg (RS) cells and variants in 100% (139/139) of HD cases, irrespective of their antigenic phenotype (T, B, non T-non B) and histologic subtype of HD. Conversely, CD40 was immunodetected on only one third (12/32; 37%) of ALC lymphoma cases and on 105 of 127 B-cell NHLs. The relative cell density of CD40 on HD cell lines (L-428, KM-H2, HDLM-2) as assessed by flow cytometry was significantly higher than on all other lymphoma cells analyzed. Engagement of CD40 by its soluble ligand (CD40L) enhanced both clonogenic capacity and colony cell survival of HD cell lines. Such effect was potentiated by interleukin-9 costimulation in KM-H2 cells. Finally, we have shown that in vitro rosetting of activated CD4+ T cells to HD cells (L-428) is mediated in part by the CD40/CD40L adhesion pathway. Our data indicate that CD40 is a useful antigen for immunodetection and identification of tumor cells in all subtypes of HD, and suggest that it may play a role in the regulation of RS cell expansion and the contact-dependent interactions of these cells with cytokine-producing T lymphocytes. |
Crennan, E.D'Costa, I.Liew, K. H.Thompson, J.Laidlaw, C.Cooper, I.Quong, G.
Lymphocyte predominant Hodgkin's disease: a clinicopathologic comparative study of histologic and immunophenotypic subtypes
| Veröffentlicht: |
1995, Int J Radiat Oncol Biol Phys, 31, 333-7 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7530700 |
| Abstract: |
PURPOSE: To compare the clinicopathologic features of the histologic and immunophenotypic subgroups of lymphocyte predominant Hodgkin's disease. METHODS AND MATERIALS: A retrospective review of 64 patients with lymphocyte predominant Hodgkin's disease treated at the Peter MacCallum Cancer Institute, Melbourne, was performed. Nodular and diffuse histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections. Immunophenotyping with monoclonal antibodies L26 (B-cell origin) and Leu M1 (Hodgkin's phenotype) were available in 36 patients. RESULTS: The estimated freedom from progression and estimated overall survival at 10 years was 74% standard error (SE 5.8%) and 85% (SE 5.2%), non-Hodgkin's respectively. There were no significant differences in freedom from progression or overall survival when nodular and diffuse histology were compared. Similarly the presence of B-cell markers did not influence prognosis. There was only one case of secondary non-Hodgkin's lymphoma. CONCLUSION: Our results are consistent with major reported series displaying no differences between any of the subgroups of lymphocyte predominant Hodgkin's disease. |
Diehl, V.Loeffler, M.Pfreundschuh, M.Ruehl, U.Hasenclever, D.Nisters-Backes, H.Sieber, M.Smith, K.Tesch, H.Geilen, W.et al.,
Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin's disease. German Hodgkins' Study Group (GHSG)
| Veröffentlicht: |
1995, Ann Oncol, 6, 901-10 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8624293 |
| Abstract: |
OBJECTIVE: It was the aim of this prospective randomized multicenter study to compare chemotherapy and radiotherapy as consolidation treatments in patients achieving complete remission (CR) after 6 cycles of doxorubicin-containing chemotherapy in advanced-stage Hodgkin's disease (HD). METHODS: A total of 288 previously untreated patients aged 18-60 years with stage IIIB or IV HD received induction chemotherapy with 3 X (COPP + ABVD). Patients achieving CR were eligible for randomisation to either 20 Gy radiotherapy to initially involved fields (RT-arm) or to an additional 1 X (Copp + ABVD) (CT-arm ). Patients with nodal PR were allocated to more intense radiotherapy (IRT-arm: 20 Gy IF, 40 Gy to persisting tumor). Four patients with persisting organ involvement after induction received salvage chemotherapy. RESULTS: Of 288 patients, 171 (59%) achieved CR after induction chemotherapy. Of these, 100 patients were successfully randomized to RT or CT. In the CT arm relapses were observed on 10 of 49 patients compared with 13 of 51 patients in the RT arm (p = n.s.). Fifty patients refused randomisation and for them a treatment was chosen, and 21 patients refused any further treatment. Of these 21 patients with no consolidation therapy, 9 relapsed, indicating an approximately 3-fold increased relapse risk compared with those receiving either of the consolidation therapies. No relapse was observed in initially involved lung or liver sites. Adverse prognostic factors for freedom from treatment failure and survival were low hemoglobin and large mediastinal mass at initial presentation. CONCLUSIONS: No statistically significant differences in treatment efficacy were detected between 20 Gy IF radiotherapy and 1X (COPP + ABVD) chemotherapy following CR after six cycles of alternating chemotherapy in patients with advanced-stage HD. However, limited observations in a non-randomized cohort indicate that patients without consolidation treatment of CR after 6 cycles of chemotherapy may have an elevated risk of relapse. |
Dubray, B.Henry-Amar, M.Meerwaldt, J. H.Noordijk, E. M.Dixon, D. O.Cosset, J. M.Thames, H. D.
Radiation-induced lung damage after thoracic irradiation for Hodgkin's disease: the role of fractionation
| Veröffentlicht: |
1995, , 36, 211-7 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: to estimate the alpha/beta ratio for damage to human lung after thoracic irradiation for Hodgkin's disease. PATIENTS AND METHODS: The criterion for lung injury was the presence of radiological changes in the vicinity of the mediastinum as assessed on regular follow-up chest X-ray examinations. Patients with supradiaphragmatic stage I-II Hodgkin's disease received mantle field irradiation as part of their treatment between 1964 and 1981 (E.O.R.T.C. protocols H1, H2, and H5). The total mediastinal doses fixed by the protocols were 35-40 Gy. The fractional doses were left to the decision of the physicians in charge: the most frequent regimens were 5 x 1.8, 5 x 2.0, 4 x 2.5 and 3 x 3.3 Gy per week. The data were fit to the linear-quadratic (L.Q.) model using time-to-injury as endpoint. RESULTS: 1048 (97%) of 1082 patients were evaluable. The mean follow-up duration was 8 years. One hundred and ninety-five cases of radiologically-visible lung damage were observed after a median interval of 6 months (range: 0-101). The 3-year actuarial probability of lung damage was 19% (95% confidence limits: 17, 21). Multivariate analysis (Cox model, stratified by protocol) showed an increased risk of damage with dose per fraction (relative risk, R.R. = 2.22 per Gy (1.75, 2.82)), the presence of systemic symptoms (R.R. = 1.53 (1.09, 2.15)), and total mediastinal dose (R.R. = 1.06 per Gy (1.01, 1.12)). Age, sex, histological type, number of involved nodal sites and radiotherapy duration did not significantly modify the risk of lung damage. The L.Q. model parameters were: alpha = 0.031 Gy-1 (0.003, 0.059), beta = 0.010 Gy-2 (0.007, 0.013), alpha/beta = 3.07 Gy (-0.23, 8.46). CONCLUSION: this low alpha/beta ratio is consistent with late effects values from animals and humans, and illustrates the influence of large fraction sizes on the occurrence of late pulmonary complications. |
Ferme, C.Bastion, Y.Lepage, E.Berger, F.Brice, P.Morel, P.Gabarre, J.Nedellec, G.Reman, O.Cheron, N.et al.,
The MINE regimen as intensive salvage chemotherapy for relapsed and refractory Hodgkin's disease
| Veröffentlicht: |
1995, Ann Oncol, 6, 543-9 |
| PubMedLink: |
|
| Abstract: |
BACKGROUND: Relapsed or refractory Hodgkin's disease (HD) patients were treated with an intensive salvage regimen (MINE) prior to high-dose therapy (HDT) with hematopoietic stem cell support. PATIENTS AND METHODS: One hundred HD patients who either failed to respond to a front-line chemotherapy regimen (induction failure, n = 41) or relapsed (untreated relapse, n = 54; resistant relapse, n = 5) were treated with the MINE regimen. Each course of MINE comprised mitoguazone 500 mg/m2 on days 1 and 5, ifosfamide 1500 mg/m2/d from day 1 to day 5, vinorelbine (Navelbine) 15 mg/m2 on days 1 and 5, and etoposide 150 mg/m2/d from day 1 to day 3. At least two courses were given at 4-week intervals. Then, 72 patients received HDT followed by hematopoietic stem cell support. RESULTS: After MINE salvage, 34 patients achieved a complete response (CR) and 39 a partial response, yielding an overall response rate of 75%. Patients with untreated relapse had a 92.5% response rate and those with resistant relapse or induction failure a 53% response rate. A total of 58 patients reached a CR at the end of all treatments; 12 of them relapsed. Sixty-six patients were alive with a median follow-up of 26 months, including 46 patients in CR. The 2-year survival rate for the entire group was 59%. By univariate analysis, patients with an interval between their last treatment and salvage longer than 12 months, untreated relapse, or good performance status at salvage are shown to have longer survivals. The main toxic effects were neutropenia, thrombocytopenia, and infectious episodes. Three patients died of MINE-related complications and three after HDT. CONCLUSION: Given early in the course of progressive HD, the MINE regimen reduced tumor burden in a high proportion of patients with relapsed or refractory disease. Responding patients further intensified with HDT have a better outcome than those who have not responded to salvage treatment. |
Herpst, J. M.Klein, J. L.Leichner, P. K.Quadri, S. M.Vriesendorp, H. M.
Survival of patients with resistant Hodgkin's disease after polyclonal yttrium 90-labeled antiferritin treatment
| Veröffentlicht: |
1995, J Clin Oncol, 13, 2394-400 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7666099 |
| Abstract: |
PURPOSE: A follow-up study was initiated of patients with Hodgkin's disease who were treated with yttrium 90-labeled antiferritin. Prescription method, pharmacokinetics, acute and late side effects, and survival were evaluated. METHODS: Patients had measurable disease and failed > or = two multiagent chemotherapy regimens previously (N = 44). All patients received 5-mCi indium 111-labeled antiferritin 2 mg intravenously and were scanned repeatedly by gamma camera. In five patients, polyclonal antiferritin (rabbit, pig, or baboon) failed to target the tumor. Thirty-nine patients were injected intravenously with 10-, 20-, 30-, 40-, or 50-mCi yttrium 90-labeled antiferritin 2 to 5 mg. Patients received between one and five cycles. Some patients were supported with 5 x 10(7) autologous bone marrow cells per kilogram. RESULTS: Yttrium 90-labeled polyclonal antiferritin does not produce immunologic, pharmacologic, or microbiologic complications in vivo. Bone marrow toxicity is the only side effect observed. Overall response rate is 20 of 39, or 51%. Two patients had stable disease. A significant positive correlation is found between blood radioactivity level 1 hour after radioimmunoconjugate administration and subsequent response of Hodgkin's disease. A dosage in millicuries per kilogram provides a higher positive correlation with blood radioactivity levels 1 hour after administration than a dosage in millicuries per square meter of body-surface area or in total millicuries. Fifty percent of patients survive for > or = 6 months. CONCLUSION: The low-dose protein used (2 to 5 mg) indicates that the high response rate is due to radiation and not to immunologic effects of the antibody. High-activity administrations followed by bone marrow transplantation are not required for tumor response. The therapeutic ratio of radiolabeled antiferritin is higher than the therapeutic ratio observed in most phase I studies of chemotherapeutic agents. This analysis does not identify a superior mode of treatment for patients with end-stage Hodgkin's disease. However, in a heavily pretreated patient population, prolonged survival is observed after relatively inexpensive treatment. Preclinical research with yttrium 90-labeled antiferritin indicates that significant increases in tumor dose can be obtained in the future without an increase in normal tissue toxicity. |
Pappa, V. I.Norton, A. J.Gupta, R. K.Wilson, A. M.Rohatiner, A. Z.Lister, T. A.
Nodular type of lymphocyte predominant Hodgkin's disease. A clinical study of 50 cases
| Veröffentlicht: |
1995, Ann Oncol, 6, 559-65 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8573534 |
| Abstract: |
BACKGROUND: Lymphocyte predominant Hodgkin's disease (LP-HD), particularly that with a nodular pattern has been suggested to constitute a distinct disorder within the spectrum of Hodgkin's disease, this issue being based on clinical, morphological and immunological observations. Furthermore, the nodular LP-HD (N-LP-HD) has been considered to differ from the diffuse subtype (D-LP-HD), although the data are conflicting. The question addressed in this study was whether the clinical course of N-LP-HD differs from that of the D-LP-HD as well as the other subtypes of Hodgkin's disease. PATIENTS AND METHODS: 90 cases diagnosed as LP-HD at St. Bartholomew's Hospital (SBH) were reviewed. The histopathological classification was based on the original Lukes and Butler criteria for classical N-LP-HD. Clinical data were retrieved from case notes and a computer database. Stage was determined by the Ann Arbor criteria. Survival and remission duration analyses were performed for the group of patients with N-LP-HD and compared with an histological control group of patients with the other subtypes of Hodgkin's disease and the cases of LP-HD that have been reclassified. RESULTS: 1. 50/90 cases (56%) originally diagnosed as N-LP-HD qualified as N-LP-HD. No case with the diffuse subtype, could be identified. Twenty-three percent of the cases were reclassified as Mixed Cellularity and 11% as Nodular Sclerosis HD, whilst 10% as non-Hodgkin's lymphomas. 2. The majority of cases (78%) presented with early stage (I + II). Bone marrow and liver involvement were rare. 3. 92% of cases achieved complete remission. Recurrence developed in only 6/46 patients within 5-12 years. A second complete remission was achieved in 5/6 (83%) cases. Further recurrences have not yet occurred. 4. The overall survival of the 50 cases with N-LP-HD was 92% at 4 years and did not differ significantly from the 40 cases that have been reclassified. Remission duration however, was significantly better for the group of N-LP-HD being 81% at 12 years. 5. Second malignancies were common and developed in 6/50 cases (12%) with N-LP-HD within 10-15 years. These included: ALL (1 case), high grade B-NHL (2 cases), squamous cell carcinoma (1 case), glioma (1 case), lung carcinoma (1 case). 6. 12/50 patients died within a period of follow-up, up to 21 years. 1/3 of the deaths was attributed to the development of second malignancy. CONCLUSIONS: The diffuse variant of LP-HD is rare, having not been seen at St. Bartholomew's Hospital during this time period. The 50 cases with N-LP-HD showed a favourable course with presentation at an early stage, good response to treatment, late recurrences and remission duration other than the other subtypes of HD. The latter could be attributable to the early stage at presentation of N-LP-HD, since the remission duration on a matching on stage analysis was superficially better in favour of N-LP-HD (p = 0.06). The indolent course of the disease in combination with the risk of second malignancy cases raises the question whether histology should be taken into consideration in the development of new protocols for HD. |
Pettersson, M.Sundstrom, C.Nilsson, K.Larsson, L. G.
The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines
| Veröffentlicht: |
1995, Blood, 86, 2747-53 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7670114 |
| Abstract: |
PU.1 is a hematopoietic transcription factor belonging to the Ets-family. It is identical to the Spi-1 oncogene, which is implicated in spleen focus-forming virus-induced murine erythroleukemias. PU.1 seems to be required for early development of multiple hematopoietic lineages, but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage-differentiation lineage. It binds the so-called Pu box, an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages. We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation, from early precursors to differentiated plasma cells. PU.1 mRNA expression and PU.1 DNA binding activity, as measured by Northern blot analysis and electrophoretic mobility shift assay, respectively, were evident in cell lines representing pro-B, pre-B, and mature B cells. We could also show Pu box-dependent transactivation of a reporter gene in transient transfections in these cell lines. In contrast, in a number of multiple myeloma cell lines, representing differentiated, plasma cell-like B cells, PU.1 DNA binding activity, mRNA expression, and Pu box-dependent transactivation were absent or detectable at a very low level. In lymphoblastoid cell lines, which exemplify an intermediate stage of B-cell differentiation, a reduced expression and activity were observed. The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines. At present, it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells. |
Pezner, R. D.Nademanee, A.Forman, S. J.
High-dose therapy and autologous bone marrow transplantation for Hodgkin's disease patients with relapses potentially treatable by radical radiation therapy
| Veröffentlicht: |
1995, Int J Radiat Oncol Biol Phys, 33, 189-94 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: A retrospective review evaluated the results of autologous bone marrow transplantation (A-BMT) for patients with relapsed Hodgkin's disease (HD) who were potentially treatable by radical radiation therapy (RRT). METHODS AND MATERIALS: Evaluated patient cases met the following criteria: initial treatment with chemotherapy (with or without involved field radiation therapy < 25 Gy); no history of bone marrow or extensive lung involvement; no current or previous evidence of systemic metastases except liver; radiation therapy used with salvage chemotherapy for prior relapse would not preclude use of RRT (e.g., > 20 Gy to spinal cord); HD at time of salvage therapy limited to lymph nodes, Waldeyer's ring, liver, spleen, direct extension sites, and/or one lung. RESULTS: There were 23 A-BMT patients treated between 1986 and 1991 who fulfilled the criteria. Three (13%) patients died from treatment-related complications and eight (35%) developed nonfatal Grade 3-4 complications. The 3-year actuarial disease-free survival rate was 61%. The 3-year disease-free survival rate was 55% for the nine patients with at least one prior disease-free interval (DFI) > 12 months, 67% for nine patients with DFI < 12 months, and 60% for five induction failure patients (p > 0.10). These results are comparable to retrospective studies of RRT results in selected relapsed HD patients. CONCLUSIONS: Long-term disease-free survival is frequently possible with either A-BMT or RRT in appropriately selected relapsed HD patients. In considering treatment options, important prognostic factors include initial stage of disease, number of prior relapses, DFI, and extent of relapsed disease. |
Schnell, R.Linnartz, C.Katouzi, A. A.Schon, G.Bohlen, H.Horn-Lohrens, O.Parwaresch, R. M.Lange, H.Diehl, V.Lemke, H.et al.,
Development of new ricin A-chain immunotoxins with potent anti-tumor effects against human Hodgkin cells in vitro and disseminated Hodgkin tumors in SCID mice using high-affinity monoclonal antibodies directed against the CD30 antigen
| Veröffentlicht: |
1995, Int J Cancer, 63, 238-44 |
| PubMedLink: |
|
| Abstract: |
The lymphocyte activation marker CD30 has been shown to be an excellent target for the immunotherapy of human Hodgkin's lymphoma. In order to develop new potent immunotoxins (ITs) against CD30, we chemically linked 6 recently described monoclonal antibodies (MAbs) via SMPT to deglycosylated ricin A-chain (dgA). Cross-blocking experiments demonstrated that these MAbs, termed Ki-2 to Ki-7, recognize 3 different clusters on the CD30 antigen: Ki-2, Ki-4, Ki-5 and Ki-7 recognize cluster A; Ki-6 recognizes cluster B; Ki-3 binds to cluster C. Staining of 29 sections of normal human organs revealed no major cross-reactivity of any MAbs tested. Binding to the CD30 antigen on L540Cy Hodgkin cells was assessed by flow cytometry, and demonstrated high affinities for Ki-2, Ki-3 and Ki-4. The concentration giving 50% of the mean fluorescence intensity (MFI50) was 0.58 micrograms/ml to 0.78 micrograms/l. MAbs Ki-5, Ki-6, and Ki-7 bound much more weakly. The staining intensity of the MAbs correlated with the cytotoxicity of the corresponding ITs. Ki-2.dgA, ki-3.dgA and Ki-4.dgA inhibited the protein synthesis of L540Cy cells by 50% at concentrations (IC50) of 3.5 x 10(-10)M to 4.0 x 10(-11)M. The most effective IT, Ki-4dgA, is 5-fold more potent than previously reported CD30 ricin A-chain ITs. Ki-4.dgA was subsequently used for the treatment of disseminated human Hodgkin's lymphoma in a SCID mouse model. The mean survival time (MST) of lymphoma-bearing SCID mice was extended from 42 days in untreated controls to more than 132 days when Ki-4.dgA was applied one day after tumor challenge. Ki-4.dgA is a new potent IT suitable for further evaluation against Hodgkin's lymphoma in man. |
Wang, T.Lasota, J.Hanau, C. A.Miettinen, M.
Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphomas but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferations is of diagnostic value
| Veröffentlicht: |
1995, APMIS, 103, 655-62 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7488387 |
| Abstract: |
The distribution of Bcl-2 oncoprotein was studied immunohistochemically in formaldehyde-fixed and paraffin-embedded reactive and neoplastic lymphoid tissue. The potential of Bcl-2 for the differential diagnosis of follicular lesions was emphasized, and the results on follicular lesions were correlated with those of polymerase chain reaction (PCR) assay of the immunoglobulin heavy chain gene rearrangement. In hyperplastic lymphoid tissue, Bcl-2 reactivity was widespread, including germinal center surroundings, scattered cells within the germinal centers, and the T-cell areas in general. Distinctively negative lymphoid populations included the majority of germinal center cells, and the negative staining pattern was maintained in cases of florid hyperplasia. In contrast, follicular lymphoma cells were consistently Bcl-2 positive. The immunohistochemical Bcl-2 reactivity of lymphoma follicles correlated with the clonal PCR amplification pattern of the immunoglobulin heavy chain gene; all Bcl-2-negative hyperplasias revealed a non-clonal pattern. Clusters of monocytoid B cells were Bcl-2 negative, whereas monocytoid B-cell lymphomas and closely related MALT lymphomas were positive. All other small cell non-Hodgkin's lymphomas of B-cell types showed nearly uniform Bcl-2 reactivity, whereas large cell B-cell lymphomas were variably positive (74%). In Hodgkin's cells, Bcl-2 reactivity was seen in the neoplastic populations of most cases of nodular sclerosis and mixed cellularity types, whereas the L&H and Reed-Sternberg cells in lymphocyte predominance Hodgkin's disease were negative in most cases. Bcl-2 immunohistochemistry thus appears very valuable in the differential diagnosis of follicular hyperplasia and neoplasia, and it may help to distinguish between reactive and neoplastic monocytoid B cells. However, Bcl-2 immunohistochemistry is not useful in the subtyping of B-cell lymphomas. |
Wickert, R. S.Weisenburger, D. D.Tierens, A.Greiner, T. C.Chan, W. C.
Clonal relationship between lymphocytic predominance Hodgkin's disease and concurrent or subsequent large-cell lymphoma of B lineage
| Veröffentlicht: |
1995, Blood, 86, 2312-20 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7662978 |
| Abstract: |
The occurrence of a large-cell lymphoma (LCL) concurrent with or subsequent to lymphocytic predominance Hodgkin's disease (LPHD) is well documented. Given the well-characterized B-cell nature of the Reed-Sternberg cell variants in LPHD, there may be a clonal relationship between the LPHD and the associated B-cell LCL. In this study, we adapted a highly sensitive, clonospecific assay to test whether the clone comprising the LCL exists in the corresponding LPHD tumor. Nine cases meeting the histologic criteria of nodular LPHD and B-cell LCL were identified, reviewed, and studied. Initially, clonality of both lesions was assessed using consensus primers to conserved regions in the IgH variable (frame-work III) and joining region genes in a polymerase chain reaction (PCR) assay. The PCR assay detected a clonal B-cell population in five of the LCLs, whereas analysis of eight cases of LPHD did not detect a dominant clone. Clonal products from the LCL were then sequenced, and clonospecific oligonucleotides were designed from the unique nucleotide sequence encoding the complementarity-determining region-III. These were then used as primers and/or probes in sensitive PCR-based assays on the corresponding LPHD tumors. In two cases, the clonospecific assay showed that the LPHD and LCL shared a common clone that was further confirmed by sequence analysis. This finding provides genotypic evidence that, at least in some cases, the LCL represents a clonal progression of LPHD. |
1996
Gajewski, J. L.Phillips, G. L.Sobocinski, K. A.Armitage, J. O.Gale, R. P.Champlin, R. E.Herzig, R. H.Hurd, D. D.Jagannath, S.Klein, J. P.Lazarus, H. M.McCarthy, P. L., Jr.Pavlovsky, S.Peterson, F. B.Rowlings, P. A.Russell, J. A.Silver, S. M.Vose, J. M.Wiernik, P. H.Bortin, M. M.Horowitz, M. M.
Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease
| Veröffentlicht: |
1996, J Clin Oncol, 14, 572-8 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To determine the outcome of HLA-identical sibling bone marrow transplants in advanced Hodgkin's disease. PATIENTS AND METHODS: We reviewed the data on 100 consecutive patients with Hodgkin's disease who received HLA-identical sibling bone marrow transplants between April 1, 1982 and August 12, 1992, reported to the International Bone Marrow Transplant Registry (IBMTR). The median interval from diagnosis to transplant was 2.5 years (range, < 1 to 14). All had advanced disease. Eighty-nine of 100 patients were not in remission at the time of transplant. Fifty had pretransplant Karnofsky scores less than 90% and 27 had active infection in the week before transplant. Patients received a variety of conditioning regimens; 45 received total-body radiation. RESULTS: The 100-day probability of acute graft-versus-host disease (GVHD) was 35% (95% confidence interval [CI], 26% to 46%); the 3-year probability of chronic GVHD was 45% (95% CI, 31% to 59%). The 3-year probability of relapse was 65% (95% CI, 50% to 78%). The 3-year probability of survival was 21% (95% CI, 14% to 30%). The 3-year disease-free survival rate was 15% (95% CI, 9% to 24%). CONCLUSION: HLA-identical sibling bone marrow transplants have a limited role in advanced Hodgkin's disease. |
Hasenclever, D.Loeffler, M.Diehl, V.
Rationale for dose escalation of first line conventional chemotherapy in advanced Hodgkin's disease. German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
1996, Ann Oncol, 7 Suppl 4, 95-8 |
| PubMedLink: |
|
| Abstract: |
Which strategy is more promising to improve the outcome of primary conventional chemotherapy in advanced Hodgkin's disease (HD): a moderate dose escalation or treatment intensification by shortening cycles? The answer generally depends on two factors: the tumour growth velocity and the chemosensitivity of the tumour. A simple mathematical model of tumour growth and chemotherapy effects was developed to quantify this dependency. The model allows to estimate the distribution of latency times (i.e., the time a tumour requires to grow from one cell to clinical detection) and the distribution of chemosensitivity in a patient population on the base of clinical data on tumour control and treatment given. The model was fitted to the data of 705 stage IIIB/IV HD patients of the German Hodgkin's Lymphoma Study Group (GHSG). The model reveals considerable heterogeneity in chemosensitivity and a significantly positive slope of the dose-response relationship at the standard treatment dose level. The model can be used to simulate the effect of various treatment escalation and intensification strategies. On the basis of such simulations we predict only small benefits (about 3% in 5-year tumour control rates) with shortening cycle intervals from 4 to 3 weeks. In contrast, we predict that a moderate dose escalation by 30% of a standard chemotherapy will lead to a potential benefit in the order of 10% in tumour control at 5 years. The presently ongoing HD9 trial of the GHSG is designed to demonstrate this effect. |
Horning, S. J.Rosenberg, S. A.Hoppe, R. T.
Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: an update
| Veröffentlicht: |
1996, Ann Oncol, 7 Suppl 4, 105-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8836420 |
| Abstract: |
From May 1989 to August 1995, 94 previously untreated patients with Hodgkin's disease stage II with bulky mediastinal involvement (n = 28) or stage III or IV (n = 66) received an abbreviated chemotherapy regimen, Stanford V, +/-radiotherapy (RT). Chemotherapy was given weekly for 12 weeks followed by consolidative RT to sites of initial bulky disease. With a median follow-up of 3 years, the actuarial 6-year survival is 93% and the freedom from progression is 89%. There have been no relapses or deaths among the 28 patients with stage II bulky mediastinal disease. Eight relapses and three deaths have occurred in the group of 66 patients with stage III-IV disease. The abbreviated chemotherapy regimen, Stanford V, in combination with RT is well tolerated and highly effective therapy for bulky, limited stage and advanced stage HD. Lower cumulative exposure to alkylating agents, doxorubicin, bleomycin and limited use of radiation is expected to improved the prospects for fertility and decrease the risks for second neoplasms and late cardiopulmonary toxicity. |
McBride, J. A.Rodriguez, J.Luthra, R.Ordonez, N. G.Cabanillas, F.Pugh, W. C.
T-cell-rich B large-cell lymphoma simulating lymphocyte-rich Hodgkin's disease
| Veröffentlicht: |
1996, Am J Surg Pathol, 20, 193-201 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8554109 |
| Abstract: |
Immunophenotypic analysis of 50 cases fulfilling the histologic criteria for mixed cellularity Hodgkin's disease disclosed nine cases with a B-cell, non-Hodgkin's phenotype (CD20+, CD15-, CD30-, EMA-). The cases were characterized by a diffuse small lymphocytic milieu, interspersed atypical large cells including classic Reed-Sternberg cells, and infrequent plasma cells, eosinophils, and L&H cells. The male:female ratio was 7:2 (aged 22-65 years, median 39 years). Three patients were Ann Arbor stage II, two stage III, and four stage IV. The patients presented with generalized lymphadenopathy (four), mesenteric lymph node involvement (two), splenomegaly (four), and bone marrow involvement (three). Four patients were treated with standard Hodgkin's disease protocols. Two attained a complete response and two a partial response; all relapsed and died. Four of five patients treated for large-cell lymphoma achieved a complete response and are currently alive without evidence of disease. The one patient with an initial partial response relapsed and died. We conclude that immunophenotypic analysis is essential in cases of histologic mixed cellularity Hodgkin's disease, especially in those with lymphocyte-rich morphology. Cases with a B-cell phenotype should be diagnosed and treated as T-cell-rich B large-cell lymphoma. |
Milpied, N.Fielding, A. K.Pearce, R. M.Ernst, P.Goldstone, A. H.
Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation
| Veröffentlicht: |
1996, J Clin Oncol, 14, 1291-6 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To compare the results achieved with myeloablative therapy followed by either allogeneic bone marrow transplantation (alloBMT) or autologous bone marrow transplantation (ABMT) for patients with Hodgkin's disease (HD). PATIENTS AND METHODS: Of more than 1,200 patients with HD reported to the European Bone Marrow Transplantation (EBMT) registry, 49 underwent alloBMT. Of these, 45 with sufficient data were matched to 45 patients who underwent ABMT. The matching criteria were sex, age at time of transplantation, stage of disease at diagnosis, bone marrow involvement at diagnosis and at transplantation, year of transplantation, disease status at time of transplantation, time from diagnosis to transplantation, and conditioning regimen with or without total-body irradiation (TBI). RESULTS: The 4-year actuarial probabilities of survival, progression-free survival (PFS), relapse, and non-relapse mortality were 25%, 15%, 61%, and 48% and 37%, 24%, 61%, and 27% after alloBMT and ABMT, respectively. The toxic death rate at 4 years was significantly higher for alloBMT patients (P = .04). For patients with sensitive disease at the time of transplantation, the 4-year actuarial probability of survival was 30% after alloBMT and 64% after ABMT (P = .007). This difference is mainly due to a higher transplant-related mortality rate after alloBMT (65% v 12%, P = .005). Acute graft-versus-host disease (aGVHD) > or = grade II was associated with a significantly lower risk of relapse, but also with a lower overall survival (OS) rate. CONCLUSION: Based on this study, alloBMT from a human leukocyte antigen (HLA)-identical sibling donor does not appear to offer any advantage when compared with ABMT. A graft-versus-Hodgkin effect is associated with > or = grade II aGVHD, but its positive effect on relapse is largely offset by its toxicity. In most circumstances, alloBMT cannot be recommended for patients with HD. |
Viviani, S.Bonadonna, G.Santoro, A.Bonfante, V.Zanini, M.Devizzi, L.Soncini, F.Valagussa, P.
Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results
| Veröffentlicht: |
1996, J Clin Oncol, 14, 1421-30 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To compare, in a prospective randomized trial, the efficacy of two different sequences of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy in untreated advanced Hodgkin's disease. PATIENTS AND METHODS: From June 1982 to September 1990, 427 consecutive previously untreated patients with pathologic stage IB, IIA bulky, IIB, III (A and B), and IV (A and B) disease were prospectively randomized to receive two different sequences of MOPP and ABVD for a minimum of six cycles followed by radiotherapy (median dose, 30 Gy) to the nodal site(s) of pretreatment bulky disease. Of 415 assessable patients, 211 received one cycle of MOPP monthly, alternated with one cycle of ABVD (alternating regimen), and 204 patients received one-half cycle of MOPP alternated with one-half cycle of ABVD within a 1-month period (hybrid regimen). RESULTS: The complete remission (CR) rate was 91% with the alternating regimen and 89% with the hybrid regimen. At 10 years, the freedom-from-progression (FFP) rate was 67% versus 69% and the overall survival (OS) rate was 74% versus 72%, respectively. After attainment of CR, 85 patients relapsed in nodal (n = 60) versus extranodal with or without nodal (n = 25) sites. In patients given consolidative radiation because of bulky lymphoma, the true recurrence rate was 13%. A total of 23 second malignancies (6%) were documented, including 11 cases of acute nonlymphocytic leukemia. No cases of congestive heart failure attributable to doxorubicin or pulmonary toxicity related to bleomycin were documented. CONCLUSION: By delivering MOPP and ABVD, it is possible to cure approximately 70% of patients with advanced Hodgkin's disease. The two different drug sequences yielded superimposable results. |
1997
Bodis, S.Kraus, M. D.Pinkus, G.Silver, B.Kadin, M. E.Canellos, G. P.Shulman, L. N.Tarbell, N. J.Mauch, P. M.
Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease
| Veröffentlicht: |
1997, J Clin Oncol, 15, 3060-6 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9294468 |
| Abstract: |
PURPOSE: The patterns of presentation, histologic pattern (nodular or diffuse), treatment, and long-term outcome were studied in patients with lymphocyte-predominant (LP) Hodgkin's disease (HD) to determine whether these patients should be treated differently than patients with other subtypes of HD. PATIENTS AND METHODS: Pathology was reviewed for 97 patients with an initial diagnosis of LPHD made between 1970 and 1993. Seventy-five patients had LPHD on review: 55 had nodular LPHD, 14 had diffuse LPHD, and six had LP histology without subclassification. There were 60 males (80%) and 15 females (20%). Sixty-six patients (88%), presented with clinical stage (CS) I or II disease. Seventy-one patients were treated at the Joint Center for Radiation Therapy (JCRT) and were considered for analysis of treatment outcome. Sixty-one of these 71 were treated with radiation (RT) alone; 17 received mantle RT alone, 27 mantle and paraaortic RT, and seven total-nodal irradiation (TNI). Ten patients with subdiaphragmatic HD received pelvic and paraaortic RT. Of the 10 remaining patients, four were treated with RT and chemotherapy (CT) and six were treated with CT alone. The median follow-up time was 10.8 years. RESULTS: The 10-year actuarial freedom-from-first-relapse (FFR) and 10-year overall survival rates for the 71 patients with LPHD treated at the JCRT were 80% and 93%, respectively. The 10-year actuarial FFR by nodular (n = 51), diffuse (n = 14), and unspecified (n = 6) histologic pattern was 74%, 100%, and 60%, respectively. Overall, 14 of 71 patients have relapsed: nine of 61 with stage IA, IB, or IIA disease and five of 10 with stage IIB to IVB disease have relapsed. The median time to relapse was 53 months. Nine of 71 patients have died. Only one death has been from HD: five patients died of second cancers, two of cardiac disease, and one of alcoholic liver cirrhosis. Of seven patients with second malignancies, five died. None of the second malignancies were non-Hodgkin's lymphoma (NHL). CONCLUSION: Patients with LPHD have different patterns of presentation, sex and age distribution, and likelihood of occult abdominal disease than patients with nodular-sclerosing (NS) or mixed-cellularity (MC) disease. The median time to relapse for LP patients was later than reported for other histologic subtypes; however, there was no pattern of continuous late relapse. With pathologic staging and standard treatment, mortality from LPHD is low; nearly all deaths have been cardiac- or second tumor-related. This suggests that less aggressive treatment for LPHD might continue to yield excellent results, while perhaps lowering the long-term risk of complications. |
Bonfante, V.Santoro, A.Viviani, S.Devizzi, L.Balzarotti, M.Soncini, F.Zanini, M.Valagussa, P.Bonadonna, G.
Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD
| Veröffentlicht: |
1997, J Clin Oncol, 15, 528-34 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9053474 |
| Abstract: |
PURPOSE: This study analyzed long-term results in patients with Hodgkin's disease who were resistant to or relapsed after first-line treatment with MOPP and ABVD. Response to salvage treatments and prognostic factors were also evaluated. PATIENTS AND METHODS: The study population included 115 refractory or relapsed patients among a total of 415 patients treated with alternating or hybrid MOPP-ABVD followed by radiotherapy (25 to 30 Gy) to initial bulky sites. The median follow-up duration of the present series was 91 months. Thirty-nine of 115 patients (34%) showed disease progression while on primary treatment (induction failures); 48 relapsed after complete remissions that lasted < or = 12 months and 28 after complete remission that lasted more than 12 months from the end of all treatments. RESULTS: At 8 years, the overall survival rate was 27%, being 54% and 28% in patients whose initial complete remission was longer or shorter than 12 months, respectively, and 8% in induction failures (P < .001). Response to first-line chemotherapy and disease extent at first progression significantly influenced long-term results, as well as the incidence and duration of complete remission. CONCLUSION: The present data confirm previous observations that showed the main prognostic factors to influence outcome after salvage treatment are response duration to first-line therapy and disease extent at relapse. The results indicate that patients who relapse after the alternating MOPP/ABVD regimen have a prognosis similar to that of patients who relapse after a four-drug regimen (MOPP or ABVD alone). Re-treatment with initial chemotherapy seems the treatment of choice for patients who relapse after an initial complete remission that lasts greater than 12 months, while the real impact of high-dose chemotherapy or new regimens should be assessed in resistant patients. |
Braeuninger, A.Kuppers, R.Strickler, J. G.Wacker, H. H.Rajewsky, K.Hansmann, M. L.
Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells
| Veröffentlicht: |
1997, Proc Natl Acad Sci U S A, 94, 9337-42 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9256483 |
| Abstract: |
Among the four subtypes of Hodgkin disease (HD), lymphocyte-predominant (LP) HD is now generally considered as a separate entity. The B cell nature of the typical Hodgkin and Reed-Sternberg (HRS) cells and their variants (L and H, lymphocytic and histiocytic cells) in LP HD has long been suspected, but the question of whether these cells represent a true tumor clone is unclear. We previously demonstrated clonal Ig gene rearrangements in one case of LP HD. In the present study, five cases of LP HD were analyzed by micromanipulation of single HRS cells from frozen tissue sections and DNA amplification of rearranged Ig heavy chain genes from those cells. Clonal V gene rearrangements harboring somatic mutations were detected in each case. In three cases ongoing somatic mutation was evident. This shows that HRS cells in LP HD are a clonal tumor population derived from germinal center B cells. The pattern of somatic mutation indicates that HRS cells in LP HD are selected for antibody expression. This, and the presence of ongoing mutation discriminates LP from classical HD. |
Carde, P.Noordijk, E.Hagenbeek, A.
Superiority of EBVP chemotherapy in combination with involved field irradiation over subtotal nodal irradiation in favorable clinical stage I-II Hodgkin´s disease: the EORTC-GPMC H7F randomized trial
| Veröffentlicht: |
1997, , 16, 13a |
| PubMedLink: |
|
| Abstract: |
|
Connors, J. M.Klimo, P.Adams, G.Burns, B. F.Cooper, I.Meyer, R. M.O'Reilly, S. E.Pater, J.Quirt, I.Sadura, A.Shustik, C.Skillings, J.Sutcliffe, S.Verma, S.Yoshida, S.Zee, B.
Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group
| Veröffentlicht: |
1997, J Clin Oncol, 15, 1638-45 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9193364 |
| Abstract: |
PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease. |
Diehl, V.Sieber, M.Ruffer, U.Lathan, B.Hasenclever, D.Pfreundschuh, M.Loeffler, M.Lieberz, D.Koch, P.Adler, M.Tesch, H.
BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin's disease. The German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
1997, Ann Oncol, 8, 143-8 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: At present, treatment results for patients with advanced-stage Hodgkin's disease remain unsatisfactory. Standard chemotherapy M(C)OPP (nitrogen mustard (cyclophosphamide). vincristine, procabazine, and prednisone). ABVD (adriamycine, bleomycine, vinblastine, and dacarbacine) or M(C)OPP/ABVD +/- radiotherapy fail to achieve long-term complete remission in 35% to 50% of these patients. The BEACOPP (bleomycin, etoposide, adriamycine, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen was developed to improve treatment results by dose intensification achieved by reduced duration of treatment (time intensification) and addition of etoposide. PATIENTS AND METHODS: Thirty untreated patients with advanced Hodgkin's disease stage IIB IV according to the Ann Arbor classification were treated with the time intensified BEACOPP regimen. Each patient was scheduled to receive eight cycles of chemotherapy with consolidating radiotherapy to sites of initial bulk disease and to residual tumor remaining after chemotherapy. RESULTS: All patients were evaluable for assessment of toxicity, treatment response, freedom from treatment failure (FFTF) and survival (SV). Of 30 treated patients, 29 patients received the intended eight cycles of BEACOPP. One patient in clinical CR, terminated the chemotherapy at his own request after six cycles and is at this time, 48 months after the end of treatment, in complete remission. Toxicity was tolerable with WHO grade 3/4 leucopenia in 28% of chemotherapy cycles and one severe (WHO grade 3) infection. No treatment-related death occurred. Cycles could generally be given on schedule. Complete remission (CR) was achieved in all but two patients (93%). At present, only one patient has relapsed. At a median follow-up of 40 months, FFTF-rate is 89% (lower confidence limit: 80%). One patient died due to progressive disease. CONCLUSION: The BEACOPP regimen is feasible at moderate hematopoeitic toxicity. With a FFTF-rate of 89% at a median follow-up of 40 months, the treatment results are very encouraging. A prospective randomised trial has been initiated to compare the BEACOPP regimen with the standard COPP/ABVD regimen in advanced-stage Hodgkin's disease. |
Horning, S. J.Chao, N. J.Negrin, R. S.Hoppe, R. T.Long, G. D.Hu, W. W.Wong, R. M.Brown, B. W.Blume, K. G.
High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices
| Veröffentlicht: |
1997, Blood, 89, 801-13 |
| PubMedLink: |
|
| Abstract: |
One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses. |
Horning, S. J.Hoppe, R. T.Mason, J.Brown, B. W.Hancock, S. L.Baer, D.Rosenberg, S. A.
Stanford-Kaiser Permanente G1 study for clinical stage I to IIA Hodgkin's disease: subtotal lymphoid irradiation versus vinblastine, methotrexate, and bleomycin chemotherapy and regional irradiation
| Veröffentlicht: |
1997, J Clin Oncol, 15, 1736-44 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: We have demonstrated that a relatively mild chemotherapy regimen, vinblastine, methotrexate, and bleomycin (VBM), and involved-field radiotherapy (IFRT) could substitute for extended-field radiotherapy in patients with favorable Hodgkin's disease (HD) who have been laparotomy-staged. The purpose of this study is to determine if VBM and regional radiotherapy can substitute for extended-field radiotherapy in favorable clinical stage (CS) I and II HD. PATIENTS AND METHODS: Seventy-eight patients with favorable CS I to II HD were randomly assigned to subtotal lymphoid irradiation (STLI) or VBM chemotherapy and regional radiotherapy. Randomization was stratified on the basis of age, sex, number of Ann Arbor sites, histology, and institution. Patients were evaluated for freedom from progressive HD, survival, and toxicity. Results were compared with the predecessor trial in pathologically staged patients. RESULTS: With a median follow-up period of 4 years, the rate of freedom from progressive HD was 92% (95% confidence interval [CI], 88% to 96%) for patients treated with STLI and 87% (95% CI, 81% to 93%) for patients treated with VBM and regional radiotherapy. Six of seven patients who relapsed are alive and in remission following successful second-line therapy. CONCLUSION: Given the caveat of a small number of patients, the results of extended-field radiotherapy and VBM and regional radiotherapy are comparable with a median follow-up period of 4 years. VBM serves as a paradigm to reduce late effects in favorable early-stage HD. We do not advocate its routine use in clinical practice, but instead encourage participation in clinical trials with the objective of maintaining efficacy while reducing toxicity in CS I and II HD. |
Horwich, A.Specht, L.Ashley, S.
Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone
| Veröffentlicht: |
1997, , 33, 848-53 |
| PubMedLink: |
|
| Abstract: |
To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse. |
Orlandi, E.Lazzarino, M.Brusamolino, E.Paulli, M.Astori, C.Magrini, U.Bernasconi, C.
Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence
| Veröffentlicht: |
1997, Leuk Lymphoma, 26, 359-68 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9322899 |
| Abstract: |
We evaluated the presenting clinical characteristics and outcome of 68 patients with nodular lymphocyte predominance Hodgkin's disease (NLP-HD), in order to delineate the pattern of evolution of the disease. The male to female ratio was 46/22 and median age 35 yrs (range, 14-86). Eight patients had a history of benign hyperplasia on lymph node biopsies performed 6 to 36 months before the diagnosis of NLP-HD. Early stage disease accounted for 75% of cases. One patient had a coexistent non-Hodgkin's lymphoma (NHL). Treatment was as follows: radiotherapy in 26, chemotherapy in 23, combined modality in 19. CR rate was 93% (63/68). 18 patients relapsed as HD and 5 developed NHL. The cumulative risk of NHL was 9% at 10 yrs. During remission, 4 patients had 5 episodes of follicular hyperplasia histologically documented. Overall survival rate was 71% at 10 yrs and and 63% at 15 yrs. Freedom from progression (FFP) declined from 67% at 5 yrs to 45% at 10 yrs, because of late relapses. Localized disease predicted for a better FFP (p = 0.01), but was not associated with a reduced risk of recurrence over time. NLP-HD is characterized by an indolent course with a constant pattern of relapse over time, also in patients with early stage disease at diagnosis. In addition to relapse as NLP-HD, patients may evolve into a NHL or develop benign lymph nodal hyperplasia. Careful long-term follow up is needed for these patients. |
Ries, L.Kosary, C.Hankey, B.
SEER Cancer Statistics Review: 1973-1994
| Veröffentlicht: |
1997, Bethesda: National Cancer Institute, , |
| PubMedLink: |
|
| Abstract: |
|
von Wasielewski, R.Werner, M.Fischer, R.Hansmann, M. L.Hubner, K.Hasenclever, D.Franklin, J.Sextro, M.Diehl, V.Georgii, A.
Lymphocyte-predominant Hodgkin's disease. An immunohistochemical analysis of 208 reviewed Hodgkin's disease cases from the German Hodgkin Study Group
| Veröffentlicht: |
1997, Am J Pathol, 150, 793-803 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9060817 |
| Abstract: |
There is wide consensus that lymphocyte predominance Hodgkin's disease (LPHD) represents a distinct clinicopathological entity of B-cell origin. However, inconsistent results of immunophenotyping studies and low confirmation rates among multi-center trials pose the question of whether LPHD really expresses heterogeneous marker profiles or whether it represents a mixture of morphologically similar entities. Among 2,836 cases reviewed by the German Hodgkin Study Group, immunophenotyping was performed on 1) cases classified or confirmed as LPHD by the reference panel (n = 104) or 2) cases not confirmed as LPHD but classified as classical HD (cHD) within the reference study trial (n = 104). In most cases, immunohistochemistry revealed a phenotype either LPHD-like (CD20+, CD15-, CD30-, CD45+) or cHD-like (CD15+, CD30+, CD20-, CD45-). In 27 cases, the immunophenotype was not fully conclusive. Additional markers for Epstein-Barr virus and CD57 and in situ hybridization for mRNA light chains allowed for a more clear-cut distinction between LPHD and cHD. However, in 25 of 104 cases, immunohistochemistry disproved the morphological diagnosis of LPHD of the panel experts, whereas 13 cases originally not confirmed as LPHD showed a LPHD-like immunopattern. Immunohistochemically confirmed LPHD cases showed a significantly better freedom from treatment failure (P = 0.033) than cHD; this was not observed in the original study classification based only on morphology (P > 0.05). Significantly better survival for LPHD cases improved from P = 0.047 (original study classification) to P = 0.0071 when classified by immunohistochemistry. Our results show that LPHD is a more immunohistochemical rather than a purely morphological diagnosis. Immunophenotyping of HD biopsies suspected of being LPHD is mandatory when a modified therapy protocol, that is, one different from those used in cHD, is discussed. |
1998
Felgar, R. E.Steward, K. R.Cousar, J. B.Macon, W. R.
T-cell-rich large-B-cell lymphomas contain non-activated CD8+ cytolytic T cells, show increased tumor cell apoptosis, and have lower Bcl-2 expression than diffuse large-B-cell lymphomas
| Veröffentlicht: |
1998, Am J Pathol, 153, 1707-15 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9846961 |
| Abstract: |
The factor(s) responsible for the reduced B cell number and increased T cell infiltrate in T-cell-rich large-B-cell lymphomas (TCRBCLs) have not been well characterized. We studied 18 TCRBCLs and 12 diffuse large-B-cell lymphomas (DLBCLs) to compare the 1) predominant T cell subpopulation(s), 2) expression of cytotoxic granule proteins (TIA-1 and granzyme B), 3) level of tumor cell apoptosis (Apoptag system, Oncor, Gaithersburg, MD), and 4) expression of Ki-67 (Mib-1) and apoptosis-related proteins (fas (CD95), bcl-2, and p53). T cells in TCRBCLs and DLBCLs were predominantly CD8+ T cells expressing alphabeta T-cell receptors and TIA-1 (16 of 18 TCRBCLs with >50% TIA-1+ small lymphocytes) but lacking granzyme B (16 of 18 TCRBCLs with <25% granzyme B+ small lymphocytes). Scattered apoptotic tumor cells (confirmed with CD20 co-labeling) were present in 15 of 18 TCRBCLs, with 14 of 15 cases having <10% apoptotic cells. No apoptotic cells were seen in 12 of 12 DLBCLs. In 16 of 16 immunoreactive TCRBCLs, <25% tumor cells were bcl-2+, whereas 6 of 12 DLBCLs had >50% bcl-2+ tumor cells. CD95 (fas) expression was also lower, with 3 of 18 (16.7%) TCRBCLs versus 4 of 12 (33%) DLBCLs having >25% CD95+ tumor cells. TCRBCLs and DLBCLs had similar levels of p53 and Ki-67 (Mib-1) expression. Thus, T cells in TCRBCLs are non-activated cytotoxic T lymphocytes (TIA-1+, granzyme B-). Tumor cell apoptosis (perhaps cytotoxic T cell mediated) may partly account for the decreased number of large (neoplastic) B cells in TCRBCLs, but other factors (ie, decreased bcl-2 expression) may also be needed. |
Glick, J. H.Young, M. L.Harrington, D.Schilsky, R. L.Beck, T.Neiman, R.Fisher, R. I.Peterson, B. A.Oken, M. M.
MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: the 8-year results of the intergroup trial
| Veröffentlicht: |
1998, J Clin Oncol, 16, 19-26 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To compare the efficacy of sequential mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) followed by doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus the MOPP/ABV hybrid regimen in advanced-stage Hodgkin's disease. PATIENTS AND METHODS: A total of 737 patients with previously untreated stages III2A, IIIB, IVA, or IVB Hodgkin's disease and patients in first relapse after radiotherapy were prospectively randomized to sequential MOPP-ABV or MOPP/ABV hybrid. Of 691 eligible patients, 344 received the sequential regimen and 347 received the hybrid. RESULTS: The overall response rate was 95%, with complete responses (CRs) in 79%: 83% on the MOPP/ABV hybrid and 75% on the sequential MOPP-ABVD arm (P = .02). With a median follow-up time of 7.3 years, the 8-year failure-free survival (FFS) rates were 64% for MOPP/ABV hybrid and 54% far sequential MOPP-ABVD (P = .01; 0.69 relative risk of failure, comparing MOPP/ABV hybrid v MOPP-ABVD). The 8-year overall survival rate was significantly better for the MOPP/ABV hybrid (79%) as compared with sequential MOPP-ABVD (71%) (P = .02; relative risk, 0.65). MOPP/ABV hybrid had significantly more life-threatening or fatal neutropenia and pulmonary toxicity than the sequential MOPP-ABVD arm, which was associated with significantly greater thrombocytopenia. Nine cases of acute myelogenous leukemia or myelodysplasia were reported on the sequential regimen as compared with only one on the hybrid (P = .01). CONCLUSION: MOPP/ABV hybrid chemotherapy was significantly more effective than sequential MOPP-ABVD. FFS and overall survival were significantly improved on the hybrid arm, which was also associated with a lower incidence of acute leukemia or myelodysplasia. |
Hasenclever, D.Diehl, V.
A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease
| Veröffentlicht: |
1998, N Engl J Med, 339, 1506-14 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9819449 |
| Abstract: |
BACKGROUND: Two thirds of patients with advanced Hodgkin's disease are cured with current approaches to treatment. Prediction of the outcome is important to avoid overtreating some patients and to identify others in whom standard treatment is likely to fail. METHODS: Data were collected from 25 centers and study groups on a total of 5141 patients treated with combination chemotherapy for advanced Hodgkin's disease, with or without radiotherapy. The data included the outcome and 19 demographic and clinical characteristics at diagnosis. The end point was freedom from progression of disease. Complete data were available for 1618 patients; the final Cox model was fitted to these data. Data from an additional 2643 patients were used for partial validation. RESULTS: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Seven factors had similar independent prognostic effects: a serum albumin level of less than 4 g per deciliter, a hemoglobin level of less than 10.5 g per deciliter, male sex, an age of 45 years or older, stage IV disease (according to the Ann Arbor classification), leukocytosis (a white-cell count of at least 15,000 per cubic millimeter), and lymphocytopenia (a lymphocyte count of less than 600 per cubic millimeter, a count that was less than 8 percent of the white-cell count, or both). The score predicted the rate of freedom from progression of disease as follows: 0, or no factors (7 percent of the patients), 84 percent; 1 (22 percent of the patients), 77 percent; 2 (29 percent of the patients), 67 percent; 3 (23 percent of the patients), 60 percent; 4 (12 percent of the patients), 51 percent; and 5 or higher (7 percent of the patients), 42 percent. CONCLUSIONS: The prognostic score we developed may be useful in designing clinical trials for the treatment of advanced Hodgkin's disease and in making individual therapeutic decisions, but a distinct group of patients at very high risk could not be identified on the basis of routinely documented demographic and clinical characteristics. |
Horie, R.Watanabe, T.
CD30: expression and function in health and disease
| Veröffentlicht: |
1998, Semin Immunol, 10, 457-70 |
| PubMedLink: |
|
| Abstract: |
CD30 was originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. Cloning and characterization of cDNAs encoding CD30 and its ligand (CD30L) established these proteins as members of the tumor necrosis factor receptor (TNFR) and tumor necrosis factor (TNF) superfamilies, respectively. Expression of CD30 is mostly restricted to virus-infected lymphocytes, neoplasms of lymphoid origin and a subset of activated T cells which produce Th2-type cytokines. The ligand is present on activated T cells, resting B cells, granulocytes, and the medulla of the thymus (epithelial cells and Hassal's corpuscles) as well as in various leukemia cells. The biological function of CD30 is pleiotropic but has come to be understood in the context of co-stimulatory signals. Signal transduction of CD30 utilizes signal transducers, TNFR-associated factors (TRAF1, 2, 3 and 5), which are shared by other TNFR family members. Mechanisms of signal transduction leading to diverse biological functions remain to be elucidated. |
Josting, A.Katay, I.Rueffer, U.Winter, S.Tesch, H.Engert, A.Diehl, V.Wickramanayake, P. D.
Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dex-BEAM)
| Veröffentlicht: |
1998, Ann Oncol, 9, 289-95 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9602263 |
| Abstract: |
BACKGROUND: Disease status before high-dose chemotherapy with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is an important predictor of transplantation-related toxicity and event-free survival (EFS) for patients with relapsed or refractory Hodgkin's disease (HD). We performed a phase II study in patients with relapsed or refractory HD to evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose chemotherapy with ABMT or PBSCT. PATIENTS AND METHODS: Twenty-six patients (median age 30, range 20-40 years) were treated with 2-4 courses of dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as salvage chemotherapy in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received high-dose chemotherapy with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide, carmustine, etoposide). RESULTS: Eighteen patients responded to Dexa-BEAM, resulting in a response rate of 69%. At the time of transplant 16 patients were in CR two patients in PR. At present 14 patients transplanted are in continuous CR (median follow-up 40 months, range 14-60 months). Two patients with PR after four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two patients with CR at the time of transplant relapsed after nine and 13 months respectively. Eight patients had rapid progressive disease after 2-4 cycles of Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis after four cycles of Dexa-BEAM. There was no transplantation-related death. CONCLUSION: These data suggests the use of high-dose chemotherapy followed by stem cell transplantation at the time of maximal response. |
Loeffler, M.Brosteanu, O.Hasenclever, D.Sextro, M.Assouline, D.Bartolucci, A. A.Cassileth, P. A.Crowther, D.Diehl, V.Fisher, R. I.Hoppe, R. T.Jacobs, P.Pater, J. L.Pavlovsky, S.Thompson, E.Wiernik, P.
Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group
| Veröffentlicht: |
1998, J Clin Oncol, 16, 818-29 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9508162 |
| Abstract: |
DESIGN: To perform a meta-analysis of all randomized trials that compared chemotherapy (CT) alone versus combined modality treatment (CT + radiotherapy [RT]) for which individual patient data could be made available. PATIENTS AND METHODS: Data on 1,740 patients treated on 14 different trials that included 16 relevant comparisons have been analysed. Eight comparisons were designed to evaluate the benefit of additional RT after the same CT (CT1 v CT1 + RT; additional RT design). Eight comparisons were designed to evaluate whether RT in a combined modality setting can be substituted by CT using either more cycles of the same CT or regimens that contain additional drugs (CT1 + CT2 v CT1 + RT or CT1 v CT2 + RT; parallel RT/CT design). RESULTS: Additional RT showed an 11% overall improvement in tumor control rate after 10 years (P = .0001; 95% confidence interval [CI], 4% to 18%). No difference could be detected with respect to overall survival (P = .57; 95% CI, -10% to 4%). In contrast, when combined modality treatment was compared with CT alone in the parallel-design trials, no difference could be detected in tumor control rates (P = .43; 95% CI, -6% to 9%), but overall survival was significantly better after 10 years in the group that did not receive RT (P = .045; 8% difference; 95% CI, 1% to 15%). There were significantly fewer fatal events among patients in continuous complete remission (relative risk [RR], 1.73; 95% CI, 1.17 to 2.53; P = .005) if no RT was given. CONCLUSION: Combined modality treatment in patients with advanced-stage Hodgkin's disease overall has a significantly inferior long-term survival outcome than CT alone if CT is given over an appropriate number of cycles. The role of RT in this setting is limited to specific indications. |
Rudiger, T.Ott, G.Ott, M. M.Muller-Deubert, S. M.Muller-Hermelink, H. K.
Differential diagnosis between classic Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and paragranuloma by paraffin immunohistochemistry
| Veröffentlicht: |
1998, Am J Surg Pathol, 22, 1184-91 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9777980 |
| Abstract: |
There are significant difficulties in the differential diagnosis of lymphomas at the interface between classic Hodgkin's lymphoma and both paragranuloma and T-cell-rich B-cell lymphoma as well as at the interface between T-cell-rich B-cell lymphoma and paragranuloma. We therefore investigated 197 cases (155 classic Hodgkin's lymphomas, 32 T-cell-rich B-cell lymphomas, and 10 paragranulomas) by paraffin immunohistochemistry. Special interest was given to cases with a B-cell phenotype of tumor cells. The reactive inflammatory infiltrate in both classic Hodgkin's lymphoma and T-cell-rich B-cell lymphoma was rich in TIA-1-positive cytolytic lymphocytes, and CD57-positive cells were rarely encountered. In contrast, in paragranuloma CD57-positive cells and small B-lymphocytes predominated the background infiltrate. The tumor cells in cases of classic Hodgkin's lymphoma were positive for CD30 in 95%, for CD15 in 75%, and for CD20 in 22%. Apart from this, vimentin was expressed in >95% of the cases. All cases of T-cell-rich B-cell lymphoma were negative for vimentin, CD30, and CD15. The reactivity of the tumor cells for CD30, CD15, CD20, and vimentin together with the background reactivity for CD57 and TIA-1 seem to reliably discriminate between the entities and should therefore help to increase the interobserver reproducibility of diagnoses in the gray zone around Hodgkin's lymphoma. |
Specht, L.Gray, R. G.Clarke, M. J.Peto, R.
Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients. International Hodgkin's Disease Collaborative Group
| Veröffentlicht: |
1998, J Clin Oncol, 16, 830-43 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9508163 |
| Abstract: |
PURPOSE: To assess the effect of more extensive radiotherapy and of adjuvant combination chemotherapy on long-term outcome of early-stage Hodgkin's disease. METHODS: In a collaborative worldwide systematic overview, individual patient data were centrally reviewed on 1,974 patients in eight randomized trials of more versus less extensive radiotherapy and on 1,688 patients in 13 trials of radiotherapy plus chemotherapy versus radiotherapy alone. Crude mortality data on 226 patients in two other trials of chemotherapy were also reviewed. RESULTS: More extensive radiotherapy reduced the risk of treatment failure (resistant or recurrent disease) at 10 years by more than one third (31.3% v 43.4% failures; P < .00001), but there was no apparent improvement in overall 10-year survival (77.1 % v 77.0% alive). The addition of chemotherapy to radiotherapy halved the 10-year risk of failure (15.8% v 32.7%; P < .00001), with a small, nonsignificant improvement in survival (79.4% v 76.5% alive). This involved a reduction of borderline significance for deaths from Hodgkin's disease (12.3% v 15.4% dead at 10 years; P = .07), which was partly counterbalanced by a nonsignificant excess of deaths from other causes (12.4% v 10.0% 10-year risk). CONCLUSION: More extensive radiotherapy fields or the addition of chemotherapy to radiotherapy in the initial treatment of early-stage Hodgkin's disease had a large effect on disease control, but only a small effect on overall survival. Recurrences could be prevented by more extensive radiotherapy or by additional chemotherapy. However, if chemotherapy had not been given initially, recurrences were generally salvageable by re-treatment with chemotherapy. Hence, less intensive primary treatment--particularly a reduction in radiotherapy fields--appears to achieve similar survival rates as more intensive treatment, although more randomized evidence is needed to confirm this. |
1999
Diehl, V.Sextro, M.Franklin, J.Hansmann, M. L.Harris, N.Jaffe, E.Poppema, S.Harris, M.Franssila, K.van Krieken, J.Marafioti, T.Anagnostopoulos, I.Stein, H.
Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease
| Veröffentlicht: |
1999, J Clin Oncol, 17, 776-83 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10071266 |
| Abstract: |
PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from other forms of Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large-scale clinical studies were lacking. This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older. Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients. Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered. |
Horning, S. J.Hoppe, R. T.Breslin, S.Baer, D. M.Mason, J.Rosenberg, S. A.
Very brief (8 week) chemotherapy (CT) and low dose (30 Gy) radiotherapy (RT) for limited stage Hodgkin´s disease (HD): preliminary results of the Stanford-Kaiser G4 study of Stanford V + RT
| Veröffentlicht: |
1999, Blood, 94, 1717a |
| PubMedLink: |
|
| Abstract: |
|
Lazarus, H. M.Rowlings, P. A.Zhang, M. J.Vose, J. M.Armitage, J. O.Bierman, P. J.Gajewski, J. L.Gale, R. P.Keating, A.Klein, J. P.Miller, C. B.Phillips, G. L.Reece, D. E.Sobocinski, K. A.van Besien, K.Horowitz, M. M.
Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry
| Veröffentlicht: |
1999, J Clin Oncol, 17, 534-45 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. CONCLUSION: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy. |
Reiser, M.Josting, A.Dias Wickramanayake, P.Draube, A.Scheid, C.Tesch, H.Wolf, J.Diehl, V.Engert, A.
Dexa-BEAM is not effective in patients with relapsed or resistant aggressive high-grade non-Hodgkin's lymphoma
| Veröffentlicht: |
1999, Leuk Lymphoma, 33, 305-12 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10221510 |
| Abstract: |
The aim of the present study was to evaluate the feasibility and response of the Dexa-BEAM regimen as a salvage therapy followed by high-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBCST) in responding patients with high-grade relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL). Sixteen pretreated patients (mean age 44, range 26-59) with relapsed (8) or resistant (8) NHL were treated with 1-4 cycles of Dexa-BEAM (dexamethasone, BCNU, etoposide, cytarabine, melphalan) in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received HDCT with PBSCT. The conditioning regimen used was BEAM. Three patients achieved CR and one patient PR, resulting in an overall response rate of 25%. Three of four responding patients underwent high-dose chemotherapy and were successfully transplanted with autologous blood stem cells. Progressive disease developed in one patient after transplantation. Myelosuppression (WHO grade III- grade IV), the major side effect, was observed in all courses of Dexa-BEAM. Myelosuppression-related infection WHO grade IV occurred in four patients. The protocol was not well tolerated in this heavily pretreated group of patients with four severe myelosuppression-related infections WHO grade IV and one treatment-related death. The overall response rate in this study is not comparable to other salvage regimens published and led to the discontinuation of the trial. In conclusion Dexa-BEAM was only effective in a minority of patients with refractory or relapsed aggressive NHL and was not useful as a cytoreductive regimen prior to HDCT. |
Rodriguez, J.Rodriguez, M. A.Fayad, L.McLaughlin, P.Swan, F.Sarris, A.Romaguera, J.Andersson, B.Cabanillas, F.Hagemeister, F. B.
ASHAP: a regimen for cytoreduction of refractory or recurrent Hodgkin's disease
| Veröffentlicht: |
1999, Blood, 93, 3632-6 |
| PubMedLink: |
|
| Abstract: |
Patients with Hodgkin's disease, which is either refractory or recurs after frontline chemotherapy with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or both regimens, generally have a poor prognosis. High-dose chemotherapy with autologous marrow or stem cell rescue (ABMT) is now a widely used salvage strategy in these patients. In this study, our objective was to determine the response rate to ASHAP (Adriamycin = doxorubicin, Solumedrol = methylprednisolone, High-dose Ara-C = cytosine arabinoside, and Platinum = cisplatinum), in a group of patients with Hodgkin's disease with such poor risk characteristics. The treatment was intended as a brief tumor reducing program before ABMT. Fifty-six patients with diagnosed relapsed or primary refractory Hodgkin's disease underwent this treatment. The program consisted of the administration of two cycles of ASHAP chemotherapy (doxorubicin 10 mg/m2/d intravenous (IV) continuous infusion (CI) over 24 hours, days 1 to 4; methylprednisolone 500 mg/d IV over 15 minutes daily for 5 days; cisplatinum 25 mg/m2/d IV CI over 24 hours, days 1 to 4; cytosine arabinoside 1.5 g/m2/d IV over 2 hours on day 5). After two courses of ASHAP the patients were evaluated for response, including a gallium scan test. Patients with progressive disease were taken off the study. Those with responding or stable disease received a third course of ASHAP, followed by consolidative treatment with ABMT. There were 19 complete responses (34% CR), 20 partial responses (36% PR), and 17 treatment failures, including 8 with minor responses and 9 with disease progression. Thus, in total there were 39 responses out of 56 patients (CR + PR = 70%). Myelosuppression was the main toxicity. There were no deaths due to toxicity. At this time, 23 patients are alive. There were 31 deaths due to disease progression and 2 due to other causes. The initial response to ASHAP before subsequent ABMT consolidation treatment correlated with survival. All 17 patients in whom ASHAP failed to achieve a response have died. The presence of B symptoms at relapse, and a duration of response to the last regimen of |
Sweetenham, J. W.Carella, A. M.Taghipour, G.Cunningham, D.Marcus, R.Della Volpe, A.Linch, D. C.Schmitz, N.Goldstone, A. H.
High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin's disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party
| Veröffentlicht: |
1999, J Clin Oncol, 17, 3101-9 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To investigate the results of high-dose therapy and autologous stem-cell transplantation (ASCT) in adults with Hodgkin's disease who do not enter remission after induction therapy, to determine overall survival (OS) and progression free survival (PFS), and to identify prognostic factors. PATIENTS AND METHODS: A retrospective analysis of 175 patients reported to the European Group for Blood and Marrow Transplantation between November 1979 and October 1995. One hundred were male and 75 were female, with a median age of 26.5 years. Responses to first-line therapy were defined as progressive disease (PD) in 88 and stable/minimally responsive disease (SD/MR) in 87. Seventy-five patients received ASCT after failure of one induction regimen. Second-line therapy was given to the remaining 100 patients. Response to second-line therapy was PD in 34 and SD/MR in 66. OS and PFS rates were determined, and prognostic factors were investigated using univariate and multivariate analyses. RESULTS: Responses to high-dose therapy and ASCT were complete response (30%), partial response (28%), no response (14%), PD (14%), and toxic death (14%). Actuarial 5-year OS and PFS rates were 36% and 32%, respectively. In univariate analysis for PFS and OS, adverse factors were use of a second-line chemotherapy regimen and interval of more than 18 months between diagnosis and ASCT. In multivariate analysis, the interval between diagnosis and ASCT maintained prognostic significance for OS. Response to the chemotherapy regimen given immediately before ASCT had no predictive value. CONCLUSION: High-dose therapy and ASCT is an effective treatment strategy for patients with Hodgkin's disease for whom induction chemotherapy fails. Outcome was equivalent for those with obvious PD or SD/MR in response to the regimen given immediately before high-dose therapy. Prospective randomized studies are required to compare this approach with conventional-dose salvage therapy. |
Vriesendorp, H. M.Quadri, S. M.Wyllie, C. T.Lai, J.Borchardt, P. E.Harris, L.Wucher, R.Askew, E.Schweichler, L.
Fractionated radiolabeled antiferritin therapy for patients with recurrent Hodgkin's disease
| Veröffentlicht: |
1999, , 5, 3324s-3329s |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10541381 |
| Abstract: |
The objective of this study was to determine the therapeutic ratio of fractionated radiolabeled immunoglobulin therapy (RIT) for patients with recurrent Hodgkin's disease. Ninety patients with recurrent Hodgkin's disease received 2 mg of yttrium-90-labeled polyclonal rabbit antihuman ferritin IgG i.v. Fifty-seven patients received a single (unfractionated) administration per treatment cycle; 11 of them were treated with 0.3 mCi/kg body weight, 39 were treated with 0.4 mCi/kg body weight, and 7 received 0.5 mCi/kg body weight per treatment cycle. Thirty-three patients had their radiolabeled immunoglobulin administration separated (fractionated) in 2 x 0.25 mCi/kg body weight (total activity, 0.5 mCi/kg). The interval between fractions was 1 week. Radioimmunoconjugates did not cause serious acute side effects. In vivo radioimmunoconjugates were stable. Human antirabbit IgG antibodies were found in 2 of 50 retreated patients (<5%). Hematological toxicity was the only side effect noted in all patients, and it was usually temporary. Response rates (RRs) were 20%, 61%, and 86% after 0.3, 0.4, or 0.5 mCi/kg unfractionated yttrium-90-labeled antiferritin. The RR for patients treated with fractionated RIT was 42%. In the fractionated RIT group, complete responses were decreased, and progressive disease increased (P < 0.05). Complete responses had a medium duration of 6 months. Median survival times were 390 days for 1 x 0.4 mCi/kg and 300 days for the 2 x 0.25 mCi/kg patient group. Fractionation did not provide the expected decrease in hematological toxicity or the expected increase in tumor RRs. |
2000
Anagnostopoulos, I.Hansmann, M. L.Franssila, K.Harris, M.Harris, N. L.Jaffe, E. S.Han, J.van Krieken, J. M.Poppema, S.Marafioti, T.Franklin, J.Sextro, M.Diehl, V.Stein, H.
European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes
| Veröffentlicht: |
2000, Blood, 96, 1889-99 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10961891 |
| Abstract: |
Paraffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determine how frequent T-cell-rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential diagnostic criteria distinguishing between the 2 lymphoma categories. For this purpose, conventionally and immunohistologically stained sections were reviewed by a panel of hematopathologists. The diagnosis of LPHD was confirmed in only 219 of the 388 assessable cases (56.5%). This low confirmation rate was due mainly to the presence of a new variant of classical Hodgkin disease (CHD), which resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and, in terms of the immunophenotype of the tumor cells, CHD and was designated nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted-as in nodular LPHD-predominantly of B cells but differed from those present in LPHD in that they represented expanded mantle zones with atrophic germinal centers. Clinically, patients with LPHD and NLRCHD showed similar disease characteristics at presentation but differed in the frequency of multiple relapses and prognosis after relapse. Patients with LPHD and NLRCHD clearly differed from patients with CHD with nodular sclerosis or mixed cellularity, as they presented with an earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD cases showed a complete or partial nodular growth pattern, their differentiation from TCRLBCL was a rare problem in the present series. (Blood. 2000;96:1889-1899) |
Anderlini, P.Giralt, S.Andersson, B.Ueno, N. T.Khouri, I.Acholonu, S.Cohen, A.Korbling, M. J.Manning, J.Romaguera, J.Sarris, A.Rodriguez,Hagemeister, F.McLaughlin, P.Cabanillas, F.Champlin, R. E.
Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin's disease
| Veröffentlicht: |
2000, Bone Marrow Transplant, 26, 615-20 |
| PubMedLink: |
|
| Abstract: |
Six patients with advanced Hodgkin's disease in which multiple conventional treatments (median prior chemotherapy regimens: seven), radiation therapy, and a prior autologous stem cell transplantation (SCT) had failed underwent allogeneic SCT following a fludarabine-based conditioning regimen. Median age was 29 years (22-30). Median time to progression after autologous SCT was 6 months (4-21). Disease status at transplant was refractory relapse (n = 3) and sensitive relapse (n = 3). Cell source was filgrastim-mobilized peripheral blood stem cells from an HLA-identical sibling (n = 4) or matched unrelated donor marrow (n = 2). Conditioning regimens were fludarabine-cyclophosphamide-antithymocyte globulin (n = 4), fludarabine-melphalan (n = 1) and fludarabine-cytarabine-idarubicin (n = 1). Myeloid recovery was prompt, with an absolute neutrophil count > or =500/microl on day 12 (11-15). Median platelet recovery to > or =20000/microl was on day 9 (0-60). Chimerism studies on day 30 indicated 100% donor-derived hematopoiesis in 4/5 evaluable patients (4/4 non-progressors). All responders (3/3) have ongoing 100% donor-derived chimerism. Acute graft-versus-host disease (GVHD) was diagnosed in 4/6 evaluable patients. Chronic GVHD was present in 2/4 evaluable patients. There were no regimen-related deaths. Overall day 100 transplant-related mortality was 2/6 (33%). Three patients have expired and three are alive and progression-free with a median follow-up of 9 months (6-26) post transplant. We conclude that allogeneic stem cell transplantation with fludarabine-based preparative regimens is feasible in these high-risk, heavily pretreated HD patients. |
Bonadonna, G.
Historical review of Hodgkin's disease
Ferme, C.Eghbali, H.Hagenbeek, A.
MOPP/ABV hybrid and irradiation in unfavorable supradiaphragmatic clinical stages I-II Hodgkin´s disease: comparison of three treatment modalities. Preliminary results of the EORTC-GELA H8-U randomized trial in 995 patients.
| Veröffentlicht: |
2000, Blood, 96, A576 |
| PubMedLink: |
|
| Abstract: |
|
Ferme, C.Sebban, C.Hennequin, C.Divine, M.Lederlin, P.Gabarre, J.Ferrant, A.Caillot, D.Bordessoule, D.Brice, P.Moullet, I.Berger, F.Lepage, E.
Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin's disease: results of the groupe d'etudes des lymphomes de l'Adulte H89 trial
| Veröffentlicht: |
2000, Blood, 95, 2246-52 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10733492 |
| Abstract: |
The treatment of advanced Hodgkin's disease (HD) with chemotherapy (CTx) alone or combined modality treatments has been controversial. In 1989, we designed a randomized study to compare 2 cycles of CTx to (sub)total nodal irradiation (RTx) as consolidation treatments for patients with stage IIIB/IV HD in complete remission (CR) or good partial response after 6 cycles of CTx. A total of 559 patients were randomized to receive 6 cycles of MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine) hybrid (n = 266) or ABVPP (n = 267). After induction treatment, 418 patients could be evaluated for the consolidation phase. With a median follow-up of 48 months, the 5-year disease-free survival estimates were 80% for 8 cycles of MOPP/ABV, 82% for 6 cycles of MOPP/ABV plus RTx, 68% for 8 cycles of ABVPP, and 75% for 6 cycles of ABVPP plus RTx (P =.01). The 5-year disease-free survival estimates did not differ between CTx and RTx, 74% and 79%, respectively (P =.07). After MOPP/ABV, the 5-year overall survival estimates did not differ between CTx and RTx, 85% and 88%, respectively (P =.2). After ABVPP, the 5-year survival estimates were 94% for CTx and 78% for RTx (P =.002). These results showed that RTx was not superior to CTx consolidation after doxorubicin-induced CR for patients with advanced HD. Because of the uncertainty of obtaining a prolonged second remission for patients relapsing after CTx and RTx and the possible long-term effects of RTx, we prefer 8 cycles of CTx as standard treatment when a CR has been achieved after 6 cycles. |
Hagenbeek, A.Eghbali, H.Fermé, C.
Three cycles of MOPP/ABV hybrid and involved-field irradiation is more effective than subtotal nodal irradiation in favorable supradiaphragmatic clinical stages I-II Hodgkin´s disease: preliminary results of the EORTC-GELA H8F randomized trial in 543 patients
| Veröffentlicht: |
2000, Blood, 96, 575a |
| PubMedLink: |
|
| Abstract: |
|
Josting, A.Reiser, M.Rueffer, U.Salzberger, B.Diehl, V.Engert, A.
Treatment of primary progressive Hodgkin's and aggressive non-Hodgkin's lymphoma: is there a chance for cure?
| Veröffentlicht: |
2000, J Clin Oncol, 18, 332-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10637247 |
| Abstract: |
PURPOSE: To determine differences in prognosis between primary progressive Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL), we retrospectively analyzed patients with progressive lymphoma who were treated with different salvage chemotherapy regimens including high-dose chemotherapy (HDCT) followed by autologous stem-cell support (ASCT). PATIENTS AND METHODS: One hundred thirty-one patients with primary progressive lymphoma (HD, n = 67; NHL, n = 64) were enrolled. Primary progressive disease was defined as disease progression during first-line chemotherapy or only transient response (complete or partial response lasting |
Josting, A.Rueffer, U.Franklin, J.Sieber, M.Diehl, V.Engert, A.
Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group
| Veröffentlicht: |
2000, Blood, 96, 1280-6 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10942369 |
| Abstract: |
To determine prognostic factors and treatment outcome, patients with primary progressive Hodgkin lymphoma (HD) registered in the database of the German Hodgkin Lymphoma Study Group (GHSG) were analyzed retrospectively. Detailed records from randomized prospective multicenter trials performed between 1988 and 1998 of 3807 patients recruited in these trials were reviewed. The median age of the 206 patients available was 34 years (range, 16-71). Fifty-seven patients (28%) in intermediate stage and 149 patients (72%) in advanced stage developed progressive disease (PD). One hundred and fifty-three patients (74%) were treated with salvage chemotherapy, 47 patients (23%) with salvage radiotherapy, and 6 patients (3%) did not receive any therapy due to rapid PD. Seventy patients (34%) were treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation. The 5-year freedom from second failure (FF2F) and overall survival (OS) for all patients were 17% and 26%, respectively. The 5-year FF2F and OS for patients treated with HDCT were 31% and 43%, respectively. In multivariate analysis low Karnofsky performance score at the time of progression (P <.0001), age above 50 years (P =.019), and failure to attain a temporary remission on first-line treatment (P =.0003) were significant adverse prognostic factors for OS. Patients with none of these risk factors had a 5-year OS of 55% compared with 0% for patients with all 3 of these unfavorable prognostic factors. Although HDCT is a reasonable option for selected patients with primary progressive HD, the majority did not receive HDCT. Interestingly, salvage radiotherapy gave promising results in patients with localized PD. (Blood. 2000;96:1280-1286) |
Kaminski, M. S.Estes, J.Zasadny, K. R.Francis, I. R.Ross, C. W.Tuck, M.Regan, D.Fisher, S.Gutierrez, J.Kroll, S.Stagg, R.Tidmarsh, G.Wahl, R. L.
Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience
| Veröffentlicht: |
2000, Blood, 96, 1259-66 |
| PubMedLink: |
|
| Abstract: |
CD20-targeted radioimmunotherapy is a promising new treatment for B-cell non-Hodgkin lymphoma (NHL). We now provide updated and long-term data on 59 chemotherapy-relapsed/refractory patients treated with iodine (131)I tositumomab in a phase I/II single-center study. Fifty-three patients received individualized therapeutic doses, delivering a specified total-body radiation dose (TBD) based on the clearance rate of a preceding dosimetric dose. Six patients received dosimetric doses only. Dose-escalations of TBD were conducted separately in patients who had or had not undergone a prior autologous stem cell transplant (ASCT) until a nonmyeloablative maximally tolerated TBD was established (non-ASCT = 75 cGy, post-ASCT = 45 cGy). Fourteen additional non-ASCT patients were treated with 75 cGy. Unlabeled antibody was given prior to labeled dosimetric and therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients responded; 20 (34%) had complete responses (CR). Thirty-five (83%) of 42 with low-grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate-grade NHL (P =.005). For all 42 responders, the median progression-free survival was 12 months, 20.3 for those with CR. Seven patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated after progression; 9 responded and 5 had a CR. Reversible hematologic toxicity was dose limiting. Only 10 patients (17%) had human anti-mouse antibodies detected. Long-term, 5 patients developed elevated thyroid-stimulating hormone levels, 5 were diagnosed with myelodysplasia and 3 with solid tumors. A single, well-tolerated treatment with iodine (131)I tositumomab can, therefore, produce frequent and durable responses in NHL, especially low-grade or transformed NHL. (Blood. 2000;96:1259-1266) |
Lieberz, D.Sextro, M.Paulus, U.Franklin, J.Tesch, H.Diehl, V.
How to restrict liver biopsy to high-risk patients in early-stage Hodgkin's disease. German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
2000, , 79, 73-8 |
| PubMedLink: |
|
| Abstract: |
Liver biopsy is an invasive diagnostic method for detecting liver involvement (LI) in Hodgkin's disease (HD). The aim of this retrospective study was to determine and evaluate a method for restricting liver biopsy to a subset of patients. Between 1988 and 1994, a total of 2,016 patients with HD were treated within the HD4-6 study protocol of the German Hodgkin's Lymphoma Study Group (GHSG). We investigated the predictive power of abdominal ultrasound (US) and computed tomography (CT), as well as of various clinical factors related to LI, using univariate and multivariate methods. LI occurred in 4.9% of all patients (99/2,016) and in 3.0% of those who, if LI were disregarded, would have been included in clinical stages I and II. In multivariate analysis the presence of LI was significantly associated with splenic involvement or infradiaphragmatic involvement, absence of mediastinal involvement, serum alkaline phosphatase (SAP) level over 230 units/l, and age over 40 years. We used these factors to define a risk score for LI. LI is very rare in patients who would otherwise be in clinical stages I or II, but knowledge of LI is important because it has therapeutic consequences. With our risk score, liver biopsy is indicated for approximately one quarter of these patients otherwise in clinical stages I or II. |
Santoro, A.Bredenfeld, H.Devizzi, L.Tesch, H.Bonfante, V.Viviani, S.Fiedler, F.Parra, H. S.Benoehr, C.Pacini, M.Bonadonna, G.Diehl, V.
Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study
| Veröffentlicht: |
2000, J Clin Oncol, 18, 2615-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10893294 |
| Abstract: |
PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin's disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m(2), was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1, 250 mg/m(2) to 1,500 mg/m(2). RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients' main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin's disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment. |
2001
Akpek, G.Ambinder, R. F.Piantadosi, S.Abrams, R. A.Brodsky, R. A.Vogelsang, G. B.Zahurak, M. L.Fuller, D.Miller, C. B.Noga, S. J.Fuchs, E.Flinn, I. W.O'Donnell, P.Seifter, E. J.Mann, R. B.Jones, R. J.
Long-term results of blood and marrow transplantation for Hodgkin's lymphoma
| Veröffentlicht: |
2001, J Clin Oncol, 19, 4314-21 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To evaluate the long-term outcome after allogeneic (allo) and autologous (auto) blood or marrow transplantation (BMT) in patients with relapsed or refractory Hodgkin's lymphoma (HL). PATIENTS AND METHODS: We analyzed the outcome of 157 consecutive patients with relapsed or refractory HL, who underwent BMT between March 1985 and April 1998. Patients < .0001) and date of BMT (HR = 0.93, P = .004) were independent predictors of EFS, whereas only disease status (HR = 0.35, P < .0001) influenced relapse. There was a trend for probability of relapse in sensitive patients to be less after allo BMT at 34% (range, 8% to 59%) versus 51% (range, 36% to 67%) for the auto patients (HR = 0.51, P = .17). There was a continuing risk of relapse or secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) for 12 years after auto BMT, whereas there were no cases of secondary AML/MDS or relapses beyond 3 years after allo BMT. CONCLUSION: There seems to be a clinical graft-versus-HL effect associated with allo BMT. Allo BMT for HL also seems to have a lower risk of secondary AML/MDS than auto BMT. Thus, allo BMT warrants continued study in HL. |
Connors, J. M.
Lymphocyte-predominant Hodgkin´s Lymphoma
| Veröffentlicht: |
2001, American Society of hematology Education program Book, , 187-190 |
| PubMedLink: |
|
| Abstract: |
|
de Wit, M.Bohuslavizki, K. H.Buchert, R.Bumann, D.Clausen, M.Hossfeld, D. K.
18FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin's lymphoma
| Veröffentlicht: |
2001, Ann Oncol, 12, 29-37 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: The value of 18FDG-PET to predict the outcome after therapy in Hodgkin's lymphoma was compared to morphologic staging and ESR. PATIENTS AND METHODS: A total of 50 concurrent 18FDG-PET and CT studies were performed in 37 patients with Hodgkin's lymphoma. ESR was evaluated 32 times after treatment was completed. RESULTS: Out of 39 residual masses found by CT 8 relapses could be proven. Out of 11 CT exams with CR 3 relapses occurred. CT turned out to show a sensitivity, specificity, PPV, NPV, and accuracy of 72%, 21%, 21%, 73%, and 32%, with respect to predict disease-free survival (DFS). 18FDG-PET was positive in 22 examinations with 10 recurrences in this group. Out of 28 negative 18FDG-PET 1 relapse developed 3 years later. 18FDG-PET turned out to show promising sensitivity, specificity, PPV, NPV, and accuracy of 91%, 69%, 46%, 96%, 74%, with respect to predict DFS. ESR was elevated in 12 studies of which 5 relapses could be proven, while out of 20 normal ESR-studies 3 relapses occurred. Thus, ESR turned out to show sensitivity, specificity, PPV, NPV, and accuracy of 63%, 71%, 42%, 85%, and 75%, with respect to predict DFS. In summary, only 18FDG-PET was able to predict DFS statistically significant. CONCLUSION: 18FDG-PET can be very useful in patients with residual masses after treatment. |
Jaffe, E.Harris, N.L.Stein, H.
Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues
| Veröffentlicht: |
2001, , , |
| PubMedLink: |
|
| Abstract: |
|
Press, O. W.LeBlanc, M.Lichter, A. S.Grogan, T. M.Unger, J. M.Wasserman, T. H.Gaynor, E. R.Peterson, B. A.Miller, T. P.Fisher, R. I.
Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease
| Veröffentlicht: |
2001, J Clin Oncol, 19, 4238-44 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11709567 |
| Abstract: |
PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life. |
Rueffer, U.Josting, A.Franklin, J.May, M.Sieber, M.Breuer, K.Engert, A.Diehl, V.
Non-Hodgkin's lymphoma after primary Hodgkin's disease in the German Hodgkin's Lymphoma Study Group: incidence, treatment, and prognosis
| Veröffentlicht: |
2001, J Clin Oncol, 19, 2026-32 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: The cumulative incidence for non-Hodgkin lymphoma's (NHL) after primary Hodgkin's disease (HD) ranges between 1% and 6%. To investigate the course of disease for secondary NHL, we retrospectively analyzed patients treated within clinical trials of the German Hodgkin's Lymphoma Study Group (GHSG) since 1981. PATIENTS AND METHODS: From 1981 to 1998, the GHSG conducted three generations of clinical trials for the treatment of primary HD involving a total of 5,406 patients. Reference histology by an expert panel was obtained for 4,104 of the patients. Data on incidence, treatment, and outcome of secondary NHL were updated in March 1999. RESULTS: At first diagnosis of HD, the pathologists rejected 114 (2.1%) of 5,520 cases initially diagnosed as HD and rediagnosed them as primary NHL. Fifty-two (0.9%) of the remaining 5,406 patients developed a secondary NHL. One patient was excluded from further analyses because of insufficient documentation. Six patients had no further therapy because of patient refusal (n = 1) or rapidly progressive disease (n = 5). For the remaining 45 patients, overall response rate was 43% (36% complete response and 7% partial response). The actuarial 2-year freedom from treatment failure (FFTF) and overall survival (OS) for all patients was 24% and 30%, respectively, and for patients with diffuse large-cell lymphoma, it was 28% and 35%, respectively. Time of occurrence of secondary NHL after first diagnosis of HD and variables employed in the age-adjusted International Prognostic Factor Index (IPFI) significantly influenced treatment outcome. CONCLUSION: In the GHSG, the incidence of secondary NHL with 0.9% is relatively low compared with previously reported series. The prognosis of secondary NHL seems dismal and is significantly influenced by time of occurrence and the age-adjusted IPFI. In a subset of patients with secondary NHL, long-term disease-free survival could be achieved. |
Torlakovic, E.Tierens, A.Dang, H. D.Delabie, J.
The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin's disease
| Veröffentlicht: |
2001, Am J Pathol, 159, 1807-14 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11696441 |
| Abstract: |
Hodgkin's disease (HD) is a lymphoproliferative disease of predominantly B-cell origin. However, the reasons for the incomplete development of the B-cell phenotype and lack of immunoglobulin expression in classical HD (cHD) have not been fully explained. We examined the expression of PU.1 in HD, an Ets-family transcription factor, which regulates the expression of immunoglobulin and other genes that are important for B-cell development. Immunohistochemistry for PU.1 was performed on 35 cases of cHD and 15 cases of lymphocyte predominance HD as well as 67 non-Hodgkin's lymphomas (NHL). Expression of PU.1 was studied by Western blotting in four cHD-derived cell lines and in five NHL cell lines. We also studied the expression of two additional B-cell transcription factors, B-cell-specific activator protein and Oct-2. Our results show a striking lack of PU.1 expression by neoplastic cells in cHD but not in lymphocyte predominance HD. Our study also confirmed that B-cell-specific activator protein but not Oct-2 is not expressed by cHD. Western blotting showed no PU.1 protein expression in the cHD-derived cell lines, with the exception of one cell line of putative monocyte/histiocyte origin. The lack of PU.1 protein expression in cHD likely contributes to the lack of immunoglobulin expression and incomplete B-cell phenotype characteristic of the Reed-Sternberg cells in cHD. |
Weihrauch, M. R.Re, D.Scheidhauer, K.Ansen, S.Dietlein, M.Bischoff, S.Bohlen, H.Wolf, J.Schicha, H.Diehl, V.Tesch, H.
Thoracic positron emission tomography using 18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease
| Veröffentlicht: |
2001, Blood, 98, 2930-4 |
| PubMedLink: |
|
| Abstract: |
Residual mediastinal masses are frequently observed in patients with Hodgkin disease (HD) after completed therapy, and the discrimination between active tumor tissue and fibrotic residues remains a clinical challenge. We studied the diagnostic value of metabolic imaging by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting active mediastinal disease and predicting relapse. Twenty-eight HD patients with a residual mediastinal mass of at least 2 cm after initial therapy or after salvage chemotherapy were prospectively assigned to 29 examinations with FDG PET and were evaluated as 29 "subjects." Patients were monitored for at least 1 year after examination and observed for signs of relapse. Median follow-up was 28 months (range, 16 to 68 months). A PET-negative mediastinal tumor was observed in 19 subjects, of whom 16 stayed in remission and 3 relapsed. Progression or relapse occurred in 6 of 10 subjects with a positive PET, whereas 4 subjects remained in remission. The negative predictive value (negative PET result and remission) at 1 year was 95%, and the positive predictive value (positive PET result and relapse) was 60%. The disease-free survival for PET-negative and PET-positive patients at 1 year was 95% and 40%, respectively. The difference was statistically significant. A negative FDG PET indicates that an HD patient with a residual mediastinal mass is unlikely to relapse before 1 year, if ever. On the other hand, a positive PET result indicates a significantly higher risk of relapse and demands further diagnostic procedures and a closer follow-up. |
2002
Bartlett, N. L.Younes, A.Carabasi, M. A.Espina, B.DiPersio, J. F.Schliebner, S. D.Siegall, C.Sing, A. P.
Phase I Study of SGN-30, a Chimeric Monoclonal Antibody (mAb), in Patients with Refractory or Recurrent CD30 + Hematologic Malignancies
| Veröffentlicht: |
2002, Blood, , 1405a |
| PubMedLink: |
|
| Abstract: |
|
Canellos, G. P.Niedzwiecki, D.
Long-term follow-up of Hodgkin's disease trial
Chisesi, T.Federico, M.Levis, A.Deliliers, G. L.Gobbi, P. G.Santini, G.Luminari, S.Linfomi, M. B.
ABVD versus stanford V versus MEC in unfavourable Hodgkin's lymphoma: results of a randomised trial
| Veröffentlicht: |
2002, Ann Oncol, 13 Suppl 1, 102-6 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12078888 |
| Abstract: |
BACKGROUND: Between January 1996 and April 2000, 355 patients with advanced Hodgkin's disease (HD) (stage II bulky disease, III and IV) were enrolled in a prospective, multicentre, randomised trial aimed at comparing the efficacy of two new promising regimens: Stanford V and MEC hybrid. ABVD was chosen as the control arm. Radiotherapy was planned at the end of induction therapy on residual masses or on sites of previous bulky lesions. One hundred and seventeen, 123 and 115 patients were treated with Stanford V, MEC and ABVD, respectively. The records of 275 enrolled patients (89 Stanford V, 88 MEC, 98 ABVD) have been reviewed and are the subject of this report. RESULTS: After induction therapy a complete response (CR) was observed in 93, 89 and 74% of patients treated with MEC, ABVD and Stanford V, respectively, with a statistically significant difference (P = 0.013) between the arms. After a median follow-up of 24 months, 16 relapses have been recorded among 196 patients who achieved a CR. Relapse rates are 16, 6 and 4% for Stanford V, ABVD and MEC, respectively (P = 0.042). The 3-year survival was 93%, without any significant difference among the arms. However, a significant difference emerged in terms of failure free survival (FFS). Patients treated with Stanford V did the worst compared with those treated with ABVD or MEC (P = 0.001). Toxicity was comparable in the three treatment arms. CONCLUSION: For this randomised study, both ABVD and MEC gave superior results to Stanford V in terms of response and FFS; MEC seems to be the best regimen in terms of relapse-free survival, even if a significant difference has not yet been achieved. Notwithstanding the short follow-up, these results seem to be very impressive in defining the best standard treatment for HD for this subset of patients. |
Franklin, J.Diehl, V.
Current clinical trials for the treatment of advanced-stage Hodgkin's disease: BEACOPP
| Veröffentlicht: |
2002, Ann Oncol, 13 Suppl 1, 98-101 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12078913 |
| Abstract: |
BACKGROUND: The bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine- prednisone (BEACOPP) regimen was developed to investigate the potential of moderate dose escalation of conventional polychemotherapy to improve the unsatisfactory treatment results in advanced-stage Hodgkin's lymphoma (HL). Following pilot studies, the randomised trial HD 9 demonstrated that BEACOPP (baseline dose) attained superior failure-free survival to COPP/ABVD, and that dose escalation made a further marked improvement. Toxicity was severe but manageable. PATIENTS AND METHODS: The current GHSG multicentre randomised trial HD 12 has a 2 x 2 factorial design in order to make two comparisons: (i) eight cycles of escalated BEACOPP (as in HD9) are compared with four escalated cycles followed by four at baseline dose; (ii) the use of additional local radiotherapy to initial bulky disease and residual disease after chemotherapy is compared with chemotherapy alone, except where radiotherapy was prescribed by a central diagnostic panel. Eligible are patients aged 16-65 years with newly diagnosed HL of stage IIB with risk factors or stage III/IV. The EORTC multicentre trial 20012 randomises patients with HL stage III/IV to either eight cycles of ABVD or eight cycles of BEACOPP (four escalated + four baseline). RESULTS: The first interim analysis (January 2001) of HD 12 with 221 evaluable patients indicated continuation of recruitment. Recruitment will end in 2002 and the final data analysis will appear in 2006. CONCLUSIONS: The BEACOPP regimen is highly effective, and moderate dose escalation makes a further worthwhile improvement in tumour control. Current trials will measure BEACOPP against the international standard and show whether the amount of chemotherapy and/or radiotherapy can be reduced. |
Glossmann, J. P.Josting, A.Pfistner, B.Paulus, U.Engert, A.
A randomized trial of chemotherapy with carmustine, etoposide, cytarabine, and melphalan (BEAM) plus peripheral stem cell transplantation (PBSCT) vs single-agent high-dose chemotherapy followed by BEAM plus PBSCT in patients with relapsed Hodgkin's disease (HD-R2)
Gomez-Almaguer, D.Ruiz-Arguelles, G. J.Lopez-MartInez, B.Estrada, E.Lobato-Mendizabal, E.Jaime-Perez, J. C.
Role of bone marrow examination in staging Hodgkin's disease: experience in Mexico
| Veröffentlicht: |
2002, Clin Lab Haematol, 24, 221-3 |
| PubMedLink: |
|
| Abstract: |
We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.). |
Horning, S. J.Hoppe, R. T.Breslin, S.Bartlett, N. L.Brown, B. W.Rosenberg, S. A.
Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial
| Veröffentlicht: |
2002, J Clin Oncol, 20, 630-7 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11821442 |
| Abstract: |
PURPOSE: To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin's disease. PATIENTS AND METHODS: One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (> or =5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up. RESULTS: With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P <.0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years. CONCLUSION: These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin's disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance. |
Josting, A.Engert, A.Diehl, V.Canellos, G. P.
Prognostic factors and treatment outcome in patients with primary progressive and relapsed Hodgkin's disease
Josting, A.Franklin, J.May, M.Koch, P.Beykirch, M. K.Heinz, J.Rudolph, C.Diehl, V.Engert, A.
New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's lymphoma study group
| Veröffentlicht: |
2002, J Clin Oncol, 20, 221-30 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11773173 |
| Abstract: |
PURPOSE: To evaluate salvage treatment outcome of patients with relapsed Hodgkin's disease (HD) and to distinguish different risk groups using identified prognostic factors. PATIENTS AND METHODS: From 4,754 patients registered in the German Hodgkin's Lymphoma Study Group (GHSG) database between 1988 and 1999, 422 patients with early (n = 170) or late (n = 252) relapsed HD were identified. One hundred seven patients (25%) relapsed after radiotherapy (RT) for early stages, 133 patients (32%) after combined-modality therapy for intermediate stages, and 182 patients (43%) after chemotherapy (CT) and RT to initial bulky disease or residual lymphoma for advanced stages. At relapse, characteristics of these 422 patients (median age, 38 years; range, 17 to 77) were stage III/IV, 45%; B symptoms, 24%; elevated erythrocyte sedimentation rate, 29%; anemia, 13%; and Karnofsky performance score, less than 90 in 13%. At first relapse, salvage treatment was RT in 13%, CT in 54%, and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) in 33%. RESULTS: Median follow-up time after relapse was 45 months. Freedom from second failure (FF2F) and overall survival (OS) were 81% and 89% for relapse after RT, 33% and 46% for early relapse after CT, and 43% and 71% for late relapse after CT, respectively. In multivariate analysis, independent risk factors were time to relapse, clinical stage at relapse, and anemia at relapse. Four subgroups with significantly different FF2F and OS were identified. The prognostic score was predictive for patients who relapsed after RT, CT with conventional CT salvage, and CT with HDCT/ASCT. CONCLUSION: In the GHSG database, time to relapse and clinical stage and anemia at relapse are relevant factors and can be used to form a prognostic score for HD patients at relapse. |
Josting, A.Rudolph, C.Reiser, M.Mapara, M.Sieber, M.Kirchner, H. H.Dorken, B.Hossfeld, D. K.Diehl, V.Engert, A.
Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease
| Veröffentlicht: |
2002, Ann Oncol, 13, 1628-35 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12377653 |
| Abstract: |
BACKGROUND: An important variable affecting outcome in relapsed and refractory Hodgkin's disease (HD) is the potential of conventional salvage chemotherapy to reduce tumor volume before high-dose chemotherapy (HDCT) and autologous stem cell transplantation. Currently, the optimal salvage chemotherapy regimen for these patients is unclear. Since dexamethasone/cisplatin/cytarabine (DHAP) given at 3-4 week intervals has been shown to be very effective in patients with relapsed aggressive non-Hodgkin's lymphoma, we evaluated this regimen given at a median of 16-day intervals in patients with relapsed and refractory HD. PATIENTS AND METHODS: Patients with relapsed or refractory HD were treated with two cycles of DHAP [dexamethasone 40 mg intravenously (i.v.) day 1-4, cisplatin 100 mg/m(2) i.v. as 24-h continuous infusion day 1, and cytarabine 2 g/m(2) i.v. 12q day 2]. Granulocyte colony-stimulating factor (G-CSF) was given at a dose of 5 micro g/kg from day 4 until day 13. Patients with partial remission (PR) or complete remission (CR) after two cycles of DHAP received sequential HDCT. RESULTS: The median age of the 102 patients included was 34 years (range 21-64 years). Forty-two percent of the patients had late relapse, 29% early relapse, 12% multiple relapse and 16% primary progressive/refractory disease. The response rate (RR) after two cycles of DHAP was 89% (21% CR, 68% PR). The RRs for patients with late, early, multiple and progressive HD were 91%, 93%, 92% and 65%, respectively. Using the chi-square test for independence, remission status (relapsed HD versus progressive HD) and stage at relapse (stage I/II versus stage III/IV) were significant factors for response to DHAP. WHO grade 4 leukocytopenia and thrombocytopenia were the main toxic- ities occurring in 43% (mean duration 1.1 days, range 0-6) and 48% (mean duration 1.4 days, range 0-11) of all courses, respectively. Neither severe infections nor treatment-related deaths occurred. Peripheral blood stem cells (PBSCs) were collected after the first cycle DHAP in eight patients. The hematopoietic progenitors showed a very rapid increase from day 10 with a synchronous and impressive peak on day 12. A mean of 6.1 x 10(6)/kg CD34(+) cells were collected per apheresis. As originally recommended in the protocol, PBSCs were routinely collected during sequential HDCT in the remaining patients. CONCLUSIONS: A brief tumor-reducing program with two cycles of DHAP given in short intervals supported by G-CSF is effective and well-tolerated in patients with relapsed and refractory HD. This regimen can be used to mobilize stem cells and select those patients with chemosensitive relapse who should subsequently be treated with HDCT. |
Ng, A. K.Bernardo, M. V.Weller, E.Backstrand, K.Silver, B.Marcus, K. C.
Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors
| Veröffentlicht: |
2002, Blood, 100, 1989-96 |
| PubMedLink: |
|
| Abstract: |
The excess risk of second malignancy after Hodgkin disease is an increasing problem. In light of the long-term data, guidelines for follow-up of survivors of Hodgkin disease need to be redefined. In this study we attempt to analyze the long-term risks and temporal trends, identify patient- and treatment-related risk factors, and determine the prognosis of patients who develop a second malignancy after radiation treatment with or without chemotherapy for Hodgkin disease. Among 1319 patients with clinical stage I-IV Hodgkin disease, 181 second malignancies and 18 third malignancies were observed. With a median follow-up of 12 years, the relative risk (RR) and absolute excess risk of second malignancy were 4.6 and 89.3/10 000 person-years. The RR was significantly higher with combined chemotherapy and radiation therapy (6.1) than with radiation therapy alone (4.0, P = .015). The risk increased with increasing radiation field size (P = .03) in patients who received combined modality therapy, and with time after Hodgkin disease. After 15 and 20 years, there was a 2.3% and 4.0% excess risk of second malignancy per person per year. The 5-year survival after development of a second malignancy was 38.1%, with the worst prognosis seen after acute leukemia and lung cancer. The excess risk of second malignancy after Hodgkin disease continues to be increased after 15 to 20 years, and there does not appear to be a plateau. Our analysis suggests that the risk may be reduced with smaller radiation fields, as are used in current trials of abbreviated chemotherapy and limited-field radiation therapy. |
Radford, J. A.Rohatiner, A. Z.Ryder, W. D.Deakin, D. P.Barbui, T.Lucie, N. P.Rossi, A.Dunlop, D. J.Cowan, R. A.Wilkinson, P. M.Gupta, R. K.James, R. D.Shamash, J.Chang, J.Crowther, D.Lister, T. A.
ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease
| Veröffentlicht: |
2002, J Clin Oncol, 20, 2988-94 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12089229 |
| Abstract: |
PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score |
Raemaekers, J.Kluin-Nelemans, H.Teodorovic, I.Meerwaldt, C.Noordijk, E.Thomas, J.Glabbeke, M.Henry-Amar, M.Carde, P.
The achievements of the EORTC Lymphoma Group. European Organisation for Research and Treatment of Cancer
| Veröffentlicht: |
2002, , 38 Suppl 4, S107-13 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11858975 |
| Abstract: |
From 1964 onwards, the EORTC Lymphoma Group has conducted seven consecutive randomised phase 3 trials on early stage Hodgkin's lymphoma aiming at increasing efficacy, while decreasing short- and long-term toxicity. Staging laparotomy is definitely abandoned and replaced by identification of prognostic subgroups based on pretreatment clinical characteristics. Event-free and overall survival significantly improved from about 50 and then 70%, in the early years, to over 80 and then 90% more recently. Radiotherapy fields have become more restricted, whereas chemotherapy has become standard. Longitudinal quality-of-life assessment has become an integral part of our studies. In advanced stages, overall outcome has improved as well with 6-year survival rates of over 80%. In aggressive types of NHL, the second generation chemotherapy schedule CHVmP-BV was superior to CHVmP. We could not show any advantage for intensification of upfront treatment with autologous stem cell transplantation. |
Robinson, S. P.Goldstone, A. H.Mackinnon, S.Carella, A.Russell, N.de Elvira, C. R.Taghipour, G.Schmitz, N.
Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation
| Veröffentlicht: |
2002, Blood, 100, 4310-6 |
| PubMedLink: |
|
| Abstract: |
We report the outcome of reduced-intensity allogeneic progenitor cell transplantation (alloPCT) for 188 patients with lymphoma from the Working Party Lymphoma of the European Group for Blood and Bone Marrow Transplantation (EBMT). The median age of the patients was 40 years, the median number of prior treatment courses was 3, and 48% of patients had undergone a prior autologous transplantation. Eighty-four percent of the patients received conditioning with fludarabine-based regimens and 10% with the BEAM (BCNU, etoposide, cytosine arabinoside, melphalan) protocol. Full donor chimerism was confirmed in 71% of 100 patients assessed. Acute graft-versus-host disease (GVHD) developed in 37% of patients and chronic GVHD in 17%. A disease response to donor leukocyte infusion (DLI) was seen in 10 of 14 patients. With a median follow-up of 283 days, the overall survival rates at 1 and 2 years were 62% and 50%, respectively. The 100-day and 1-year transplantation-related mortality (TRM) rates were 12.8% and 25.5%, respectively, and were significantly worse for older patients. The probability of disease progression at 1 year for patients with chemoresistant and chemosensitive disease were 75% and 25%, respectively (P =.001). The progression-free survival at 1 year was 46% and was significantly better for those with chemosensitive disease, Hodgkin disease (HD), and low-grade non-Hodgkin lymphoma (NHL). Patients with high-grade NHL, mantle cell lymphoma, or chemoresistant disease had a poor outcome. Reduced-intensity progenitor cell transplantation is associated with a reduced TRM and may control advanced HD and low-grade NHL. A longer period of follow-up is required to determine the benefit of DLI and the graft-versus-lymphoma effect. |
Rudiger, T.Gascoyne, R. D.Jaffe, E. S.de Jong, D.Delabie, J.De Wolf-Peeters, C.Poppema, S.Xerri, L.Gisselbrecht, C.Wiedenmann, S.Muller-Hermelink, H. K.
Workshop on the relationship between nodular lymphocyte predominant Hodgkin's lymphoma and T cell/histiocyte-rich B cell lymphoma
Schlembach, P. J.Wilder, R. B.Jones, D.Ha, C. S.Fayad, L. E.Younes, A.Hagemeister, F.Hess, M.Cabanillas, F.Cox, J. D.
Radiotherapy alone for lymphocyte-predominant Hodgkin's disease
| Veröffentlicht: |
2002, Cancer J, 8, 377-83 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12416895 |
| Abstract: |
PURPOSE: The purpose of the study was to analyze the results with radiotherapy alone in a select group of asymptomatic adults with nonbulky, early-stage lymphocyte-predominant Hodgkin's disease. PATIENTS AND METHODS: Between 1963 and 1995, 36 patients with nonbulky stage IA (N = 27) or IIA (N = 9) supradiaphragmatic (N = 27) or subdiaphragmatic (N = 9) lymphocyte-predominant Hodgkin's disease were treated with radiotherapy alone. Eleven of the patients underwent laparotomy. Limited-field radiotherapy involving only one side of the diaphragm and extended-field radiotherapy encompassing both sides of the diaphragm were used in 28 and 8 cases, respectively. Median dose to involved areas was 40.0 Gy given daily in 20 2.0-Gy fractions. Salvage treatmentconsisted of MOPP (mechlorethamine, vincristine, prednisone, procarbazine), CVPP/ABDIC (cyclophosphamide, vinblastine, procarbazine and prednisone/doxorubicin, bleomycin, dacarbazine, lomustine, and prednisone), or ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy and/or involved-field radiotherapy. RESULTS: Median follow-up was 8.8 years (range, 3.0-34.4 years). None of the 15 patients with supradiaphragmatic disease who received limited-field radiotherapy to regions that did not include the mediastinal or hilar nodes subsequently experienced relapse there. Only one of 20 patients who received supradiaphragmatic limited-field radiotherapy alone experienced relapse in the paraaortic nodes or spleen. The 5-year relapse-free and overall survival rates for the 20 patients with stage IA lymphocyte-predominant Hodgkin's disease treated with involved-field or regional radiotherapy were 95% and 100%, respectively. There were no cases of severe or life-threatening cardiac toxicity. No solid tumors have been observed in-field in patients treated with limited-field radiotherapy, even though they have been followed up longer than those treated with extended-field radiotherapy (median follow-up, 11.6 vs 5.5 years); two solid tumors have developed in-field in patients who received extended-field radiotherapy. DISCUSSION: Involved-field or regional radiotherapy alone may be adequate in stage IA lymphocyte-predominant Hodgkin's disease patients. Longer follow-up will help to more clearly define the risks of cardiac toxicity and solid tumors that result from involved-field or regional radiotherapy, which appear to be low based on follow-up to date. |
Schmitz, N.Pfistner, B.Sextro, M.Sieber, M.Carella, A. M.Haenel, M.Boissevain, F.Zschaber, R.Muller, P.Kirchner, H.Lohri, A.Decker, S.Koch, B.Hasenclever, D.Goldstone, A. H.Diehl, V.
Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial
| Veröffentlicht: |
2002, Lancet, 359, 2065-71 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12086759 |
| Abstract: |
BACKGROUND: High-dose chemotherapy followed by transplantation of autologous haemopoietic stem cells (BEAM-HSCT) is frequently used to treat patients with relapsed Hodgkin's disease. We aimed to compare this treatment with conventional aggressive chemotherapy without stem-cell transplantation (Dexa-BEAM). METHODS: 161 patients between 16 and 60 years of age with relapsed Hodgkin's disease were randomly assigned two cycles of Dexa-BEAM (dexamethasone and carmustine, etoposide, cytarabine, and melphalan) and either two further courses of Dexa-BEAM or high-dose BEAM and transplantation of haemopoietic stem cells. Only patients with chemosensitive disease (complete or partial remission after two courses of Dexa-BEAM) proceeded to further treatment. The primary endpoint was freedom from treatment failure for patients with chemosensitive disease. Analysis was per protocol. FINDINGS: 17 patients were excluded from the study after randomisation (ten given Dexa-BEAM and seven given BEAM-HSCT). Median follow-up was 39 months (IQR 3-78). Freedom from treatment failure at 3 years was significantly better for patients given BEAM-HSCT (55%) than for those on Dexa-BEAM (34%; difference -21%, 95% CI -39.87 to -2.13; p=0.019). Overall survival of patients given either treatment did not differ significantly. INTERPRETATION: High-dose BEAM and transplantation of haemopoietic stem cells improves freedom from treatment failure in patients with chemosensitive first relapse of Hodgkin's disease irrespective of length of initial remission. |
Sieber, M.Franklin, J.Tesch, H.Rueffer, U.Brillant, C.Reineke, T.
Two cycles of ABVD plus extended field radiotherapy is superior to radiotherapy alone in early stage Hodgkin´s disease: results of the German Hodgkin´s Lymphoma Study Group (GHSG) trial HD7
| Veröffentlicht: |
2002, Blood, 100, 341a |
| PubMedLink: |
|
| Abstract: |
|
Sieber, M.Tesch, H.Pfistner, B.Rueffer, U.Lathan, B.Brosteanu, O.Paulus, U.Koch, T.Pfreundschuh, M.Loeffler, M.Engert, A.Josting, A.Wolf, J.Hasenclever, D.Franklin, J.Duehmke, E.Georgii, A.Schalk, K. P.Kirchner, H.Doelken, G.Munker, R.Koch, P.Herrmann, R.Greil, R.Anselmo, A. P.Diehl, V.
Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5
| Veröffentlicht: |
2002, J Clin Oncol, 20, 476-84 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: To investigate whether treatment results in intermediate-stage Hodgkin's lymphoma can be improved by rapid application of non-cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks. PATIENTS AND METHODS: From January 1988 to January 1993, 996 patients in stage I or II Hodgkin's lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin's lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy. RESULTS: Both regimens produced similar rates for treatment responses (complete remission, 93% v 94%), freedom from treatment failure (80% v 79%), and overall survival (88% for both regimens) at a median follow-up time of 7 years. Most serious toxicities during chemotherapy were similar in both regimens. However, World Health Organization grade 3 and 4 leukocytopenia occurred significantly more frequently in the COPP/ABV/IMEP arm (53% v 44% of patients; P =.010). There were no differences in the number of serious infections and toxic deaths during therapy. The number of second malignancies was also the same in both arms (22 each). CONCLUSION: Alternating COPP/ABVD and rapid alternating COPP/ABV/IMEP in combination with extended-field radiotherapy are equally effective in intermediate-stage Hodgkin's lymphoma and produce excellent long-term treatment results. |
Sureda, A.Schmitz, N.
Role of allogeneic stem cell transplantation in relapsed or refractory Hodgkin's disease
| Veröffentlicht: |
2002, Ann Oncol, 13 Suppl 1, 128-32 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12078894 |
| Abstract: |
Little information is available regarding allogeneic stem cell transplantation (alloSCT) and Hodgkin's disease (HD). Autologous stem cell transplantation (autoSCT) is usually preferred to alloSCT due to its widespread availability, lack of the immunological problems intrinsic to the development of graft-versus-host disease (GvHD), and the infrequent bone marrow involvement present in HD patients undergoing high-dose chemotherapy/radiotherapy. AlloSCT has been associated with a high transplant-related mortality (TRM) in patients with HD due to a high incidence of GvHD and of fatal infectious events after transplantation. The poor outcome of these patients after alloSCT may reflect in part the advanced status of the disease at transplantation and the poor performance status of the patient population allografted. Furthermore, the high TRM present in t h e conventional alloSCT setting hasnever allowed a proper evaluation of a possible graft-versus-Hodgkin's effect. In an effort to reduce the TRM associated with alloSCT, low-intensity regimens have been developed; the curative potential of these protocols would rely on the graft-versus-leukemia effect of the allogeneic infusion more than in the conditioning regimen per se. Although the number of HD patients allografted with reduced-intensity protocols is low and the follow-up still short, TRM seems lower than in the conventional allograft setting despite a similar incidence of acute GvHD (aGvHD). Overall and progression-free survival seem promising, and patients developing aGvHD after transplantation or donor lymphocyte infusions seem to be at a lower risk of relapse than those not presenting this complication. |
Wahl, A. F.Klussman, K.Thompson, J. D.Chen, J. H.Francisco, L. V.Risdon, G.Chace, D. F.Siegall, C. B.Francisco, J. A.
The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease
| Veröffentlicht: |
2002, Cancer Res, 62, 3736-42 |
| PubMedLink: |
|
| Abstract: |
The leukocyte activation marker CD30 is highly expressed on the Reed Sternberg cells of Hodgkin's disease (HD). On normal tissues, CD30 has a restricted expression profile limited to activated T cells, activated B cells, and activated natural killer cells. This expression profile makes CD30 an ideal target for monoclonal antibody (mAb)-based therapies of Hodgkin's disease. CD30 mAbs have been shown to be effective in in vitro and in vivo models of hematologic malignancies such as anaplastic large cell lymphoma, yet these mAb have not been efficacious in HD models. We have found that a mAb against CD30, AC10, was able to inhibit the growth of HD cell lines in vitro. To generate a more clinically relevant molecule, the variable regions from AC10 were cloned into an expression construct containing the human gamma1 heavy chain and kappa light chain constant regions. The resulting chimeric antibody, designated SGN-30, retained the binding and in vitro growth-inhibitory activities of the parental antibody. Treatment of HD cell lines with SGN-30 in vitro resulted in growth arrest in the G(1) phase of the cell cycle and DNA fragmentation consistent with apoptosis in the HD line L540cy. Severe combined immunodeficient mouse xenograft models of disseminated HD treated with SGN-30 produced significant increases in survival. Similarly, xenograft models of localized HD demonstrated dose-dependent reduction in tumor mass in response to SGN-30 therapy. SGN-30 is being developed for the treatment of patients who have HD that is refractory to initial treatment or who have relapsed and have limited therapeutic options. |
Wilder, R. B.Schlembach, P. J.Jones, D.Chronowski, G. M.Ha, C. S.Younes, A.Hagemeister, F. B.Barista, I.Cabanillas, F.Cox, J. D.
European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease
| Veröffentlicht: |
2002, Cancer, 94, 1731-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11920535 |
| Abstract: |
BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the literature regarding the role of chemotherapy in patients with early-stage LPHD. The objective of this study was to examine recurrence free survival (RFS), overall survival (OS), and patterns of first recurrence in patients with LPHD who were treated with radiotherapy alone or with chemotherapy followed by radiotherapy. METHODS: From 1963 to 1996, 48 consecutive patients ages 16-49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients) or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or favorable (F; n = 43 patients) LPHD, according to the European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone (n = 37 patients) or received chemotherapy followed by radiotherapy (n = 11 patients). The percentages of patients with VF disease (11% vs. 9% in the radiotherapy group vs. the chemotherapy plus radiotherapy group, respectively) or F disease (89% vs. 91%, respectively) within the two treatment groups were similar (P = 1.00). A median of three cycles of chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) was given initially to six patients and five patients, respectively. A median total radiotherapy dose of 40 grays (Gy) given in daily fractions of 2.0 Gy was delivered to both treatment groups. RESULTS: The median follow-up was 9.3 years, and 98% of patients were observed for > or = 3.0 years. RFS was similar for patients who were treated with radiotherapy alone and patients who were treated with chemotherapy followed by radiotherapy (10-year survival rates: 77% and 68%, respectively; P = 0.89). The OS rate also was similar for the two groups (10-year survival rates: 90% and 100%, respectively; P = 0.43). MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside of the radiotherapy fields. CONCLUSIONS: MOPP or NOVP chemotherapy did not improve RFS or OS significantly in patients with VF or F LPHD, although the statistical power was limited. Ongoing clinical trials will help to clarify the role of a watch-and-wait strategy or systemic therapy, including anthracycline (epirubicin or doxorubicin), bleomycin, and vinblastine-based chemotherapy or antibody-based approaches, in the treatment of these patients. |
2003
Aleman, B. M.Raemaekers, J. M.Tirelli, U.Bortolus, R.van 't Veer, M. B.Lybeert, M. L.Keuning, J. J.Carde, P.Girinsky, T.van der Maazen, R. W.Tomsic, R.Vovk, M.van Hoof, A.Demeestere, G.Lugtenburg, P. J.Thomas, J.Schroyens, W.De Boeck, K.Baars, J. W.Kluin-Nelemans, J. C.Carrie, C.Aoudjhane, M.Bron, D.Eghbali, H.Smit, W. G.Meerwaldt, J. H.Hagenbeek, A.Pinna, A.Henry-Amar, M.
Involved-field radiotherapy for advanced Hodgkin's lymphoma
| Veröffentlicht: |
2003, N Engl J Med, 348, 2396-406 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12802025 |
| Abstract: |
BACKGROUND: The use of involved-field radiotherapy after chemotherapy for advanced Hodgkin's lymphoma is controversial. METHODS: We randomly assigned patients with previously untreated stage III or IV Hodgkin's lymphoma who were in complete remission after hybrid chemotherapy with mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP-ABV) to receive either no further treatment or involved-field radiotherapy. Radiotherapy consisted of 24 Gy to all initially involved nodal areas and 16 to 24 Gy to all initially involved extranodal sites. Patients in partial remission were treated with 30 Gy to nodal areas and 18 to 24 Gy to extranodal sites. RESULTS: Of 739 patients, 421 had a complete remission; 161 of these patients were assigned to no further treatment, and 172 to involved-field radiotherapy. The median follow-up was 79 months. The five-year event-free survival rate was 84 percent in the group that did not receive radiotherapy and 79 percent in the group that received involved-field radiotherapy (P=0.35). The five-year overall survival rates were 91 and 85 percent, respectively (P=0.07). Among the 250 patients in partial remission after chemotherapy, the five-year event-free and overall survival rates were 79 and 87 percent, respectively. CONCLUSIONS: Involved-field radiotherapy did not improve the outcome in patients with advanced-stage Hodgkin's lymphoma who had a complete remission after MOPP-ABV chemotherapy. Radiotherapy may benefit patients with a partial response after chemotherapy. |
Baetz, T.Belch, A.Couban, S.Imrie, K.Yau, J.Myers, R.Ding, K.Paul, N.Shepherd, L.Iglesias, J.Meyer, R.Crump, M.
Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group
| Veröffentlicht: |
2003, Ann Oncol, 14, 1762-7 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14630682 |
| Abstract: |
BACKGROUND: Gemcitabine (difluorodeoxycytidine) is active as a single agent in Hodgkin's disease and has been used successfully in combination with cisplatin to treat a variety of solid tumors. PATIENTS AND METHODS: We evaluated the combination of gemcitabine/dexamethasone/cisplatin (GDP) as salvage chemotherapy in 23 patients with relapsed or refractory Hodgkin's disease (median age 36 years, range 19-57). Treatment consisted of gemcitabine 1000 mg/m(2) intravenously on days 1 and 8, dexamethasone 40 mg orally days 1-4 and cisplatin 75 mg/m(2) on day 1, every 21 days as an outpatient. Response was assessed following two cycles of treatment. RESULTS: There were four complete responses and 12 partial responses for a response rate of 69.5% (95% confidence interval 52% to 87%); the remaining seven patients had stable disease and no patient progressed on treatment. All patients had successful stem cell mobilization and underwent transplantation with a median 10.6 x 10(6) CD34+ cells/kg. Hematological toxicity from GDP was mild (grade 3 neutropenia 8.6%, grade 3 thrombocytopenia 13%). CONCLUSIONS: In summary, GDP is an active regimen for patients with relapsed or refractory Hodgkin's disease. The response rate is similar to the rates of other current salvage regimens, it can be given to outpatients with tolerable toxicity and it does not inhibit the mobilization of autologous stem cells. |
Bhatia, S.Yasui, Y.Robison, L. L.Birch, J. M.Bogue, M. K.Diller, L.DeLaat, C.Fossati-Bellani, F.Morgan, E.Oberlin, O.Reaman, G.Ruymann, F. B.Tersak, J.Meadows, A. T.
High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin's disease: report from the Late Effects Study Group
| Veröffentlicht: |
2003, J Clin Oncol, 21, 4386-94 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: We present an update of a previously reported Late Effects Study Group cohort of 1,380 children with Hodgkin's disease (HD) diagnosed between 1955 and 1986 in patients aged 16 years or younger. We describe the pattern and incidence of subsequent neoplasms (SNs) occurring with extended follow-up. PATIENTS AND METHODS: Median age at diagnosis of HD was 11.7 years (range, 0.3 to 16.9 years) and at last follow-up was 27.8 years. Median length of follow-up was 17.0 years. RESULTS: An additional 103 SNs were ascertained (total SNs = 212). The cohort was at an 18.5-fold increased risk of developing SNs compared with the general population (standardized incidence ratio [SIR], 18.5, 95% CI, 15.6 to 21.7). The cumulative incidence of any second malignancy was 10.6% at 20 years, increasing to 26.3% at 30 years; and of solid malignancies was 7.3% at 20 years, increasing to 23.5% at 30 years. Breast cancer was the most common solid malignancy (SIR, 56.7). Other commonly occurring solid malignancies included thyroid cancer (SIR, 36.4), bone tumors (SIR, 37.1), and colorectal (SIR, 36.4), lung (SIR, 27.3), and gastric cancers (SIR, 63.9). Risk factors for solid tumors included young age at HD and radiation-based therapy. Thirty-two patients developed third neoplasms, with the cumulative incidence approaching 21% at 10 years from diagnosis of second malignancy. CONCLUSION: Additional follow-up of this large cohort of HD survivors documents an increasing occurrence of known radiation-associated solid tumors, (breast and thyroid cancers), as well as emergence of epithelial neoplasms common in adults, (colon and lung cancers) at a younger age than expected in the general population, necessitating ongoing surveillance of this high risk population. |
Borchmann, P.Treml, J. F.Hansen, H.Gottstein, C.Schnell, R.Staak, O.Zhang, H. F.Davis, T.Keler, T.Diehl, V.Graziano, R. F.Engert, A.
The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma
| Veröffentlicht: |
2003, Blood, 102, 3737-42 |
| PubMedLink: |
|
| Abstract: |
CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma. To overcome the limitations from currently available murine anti-CD30 monoclonal antibodies (mAbs), a new fully human anti-CD30 antibody was generated. Binding properties were evaluated by recombinant CD30 capture enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell-sorter (FACS) flow cytometry. Activity of this new mAb was assessed in vitro using growth inhibition and antibody-dependent cellular cytotoxicity (ADCC) assays on several cell lines. In vivo activity was determined in a solid as well as in a disseminated xenografted model of HL in severe combined immunodeficiency (SCID) mice. The mAb 5F11 showed specific binding to CD30 (cluster A). The ADCC assays indicated dose-dependent lysis of L540 cells when 5F11 was combined with human effector cells. Upon cross-linking in vitro, 5F11 inhibited the growth of CD30-expressing cell lines. In vivo, treatment with 5F11 induced a marked growth delay or even a complete regression of established xenografted HL in SCID mice. In the disseminated HL model, a high proportion of 5F11-treated mice experienced long-term survival. The new human anti-CD30 monoclonal antibody 5F11 shows promise as a means of CD30-targeted immunotherapy of malignant lymphomas. Based on these results, a clinical phase 1 study in patients with refractory CD30+ lymphoma has been initiated. |
Boudova, L.Torlakovic, E.Delabie, J.Reimer, P.Pfistner, B.Wiedenmann, S.Diehl, V.Muller-Hermelink, H. K.Rudiger, T.
Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma
| Veröffentlicht: |
2003, Blood, 102, 3753-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12881319 |
| Abstract: |
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) are distinct tumors and are treated differently. They are linked by a morphologic and probably a biologic continuum, which renders the differential diagnosis difficult. To develop criteria to distinguish the entities along the morphologic continuum, we correlated the lymph node architecture and immunophenotype of both tumor cells and reactive components of 235 neoplasms in the spectrum of NLPHL and T/HRBCL with clinical data. Two hundred and eighteen cases fitted the World Health Organization (WHO) criteria of NLPHL (139) or T/HRBCL (79). While tumor cells in both entities were immunophenotypically similar, background composition differed: in NLPHL small B cells and CD3+CD4+CD57+ T cells were common, whereas in T/HRBCL, CD8+ cytotoxic T cells and histiocytes dominated. Follicular dendritic cells (FDCs) formed expanded meshworks in NLPHL, whereas they were absent in T/HRBCL. Seventeen cases represented a gray zone: within FDC meshworks, neoplastic B cells resided in a background depleted of small B cells but rich in T cells and histiocytes. Tumor cells either were loosely scattered or formed clusters, thus resembling areas of either T/HRBCL or inflammatory diffuse large BCL (DLBCL) within the nodules. Patients with these NLPHLs with T-cell/histiocyte-rich nodules presented at a high stage and with B symptoms, as in T/HRBCL, but had an excellent survival, as in NLPHL. This morphologic pattern suggests a biologic continuum between NLPHL and T/HRBCL. |
DeVita, V. T., Jr.
A selective history of the therapy of Hodgkin's disease
Diehl, V.Franklin, J.Pfreundschuh, M.Lathan, B.Paulus, U.Hasenclever, D.Tesch, H.Herrmann, R.Dorken, B.Muller-Hermelink, H. K.Duhmke, E.Loeffler, M.
Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease
| Veröffentlicht: |
2003, N Engl J Med, 348, 2386-95 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12802024 |
| Abstract: |
BACKGROUND: Faced with unsatisfactory results of treatment for advanced Hodgkin's disease, we investigated three combinations of chemotherapy. METHODS: From 1993 to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed Hodgkin's disease in unfavorable stage IIB or IIIA or stage IIIB or IV were randomly assigned to receive eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP); or increased-dose BEACOPP, each followed by local radiotherapy when indicated. Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results. RESULTS: For the final analysis, 1195 of 1201 patients could be evaluated: 260 in the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The rate of freedom from treatment failure at five years was 69 percent in the COPP-ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose BEACOPP group (P=0.04 for the comparison of the COPP-ABVD group with the BEACOPP group and P<0.001 for the comparison of the increased-dose BEACOPP group with the COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall survival were 83 percent, 88 percent, and 91 percent, respectively (P=0.16 for the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the comparison of the BEACOPP group with the increased-dose BEACOPP group, and P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BEACOPP group). Rates of early progression were significantly lower with increased-dose BEACOPP than with COPP-ABVD or standard BEACOPP. CONCLUSIONS: Increased-dose BEACOPP resulted in better tumor control and overall survival than did COPP-ABVD. |
Diehl, V.Stein, H.Hummel, M.Zollinger, R.Connors, J. M.
Hodgkin's lymphoma: biology and treatment strategies for primary, refractory, and relapsed disease
| Veröffentlicht: |
2003, , , 225-47 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14633784 |
| Abstract: |
Hodgkin's lymphomas belong to the most curable tumor diseases in adults. About 80% of patients in all anatomical stages and of all histological subtypes can be cured with modern treatment strategies. In spite of the great clinical progress, the pathogenesis of this peculiar lymphoproliferative entity has not been elucidated completely up until now. In Section I Drs. Stein, Hummel, and Zollinger describe the different pro-proliferative and antiapoptotic pathways and molecules involved in the transformation of the germinal center B-lymphocyte to the malignant Hodgkin-Reed-Sternberg cell. They use a comprehensive gene expression profiling (Affymetrix gene chip U133A) on B- and T-Hodgkin cell lines and state that the cell of origin is not the dominant determinant of the Hodgkin cell phenotype, but the transforming event. H-RS cells lack specific functional markers (B-T-cell receptors) and physiologically should undergo apoptosis. Why they do not is unclear and a matter of intensive ongoing research. In Section II Dr. Diehl summarizes the commonly used primary treatment strategies adapted to prognostic strata in early, intermediate and advanced anatomical stages using increasing intensities of chemotherapy (two, four, eight courses of chemotherapy such as ABVD) and additive radiation with decreased doses and field size. ABVD is without doubt the gold standard for early and intermediate stages, but its role as the standard regimen for advanced stages is challenged by recent data with time- and dose-intensified regimens such as the escalated BEACOPP, demonstrating superiority over COPP/ABVD (equivalent to ABVD) for FFTF and OS in all risk strata according to the International Prognostic Score. In Section III, Dr. Connors states that fortunately there is a considerably decreased need for salvage strategies in Hodgkin's lymphomas since primary treatment results in a more than 80% tumor control. Nevertheless, a significant number of patients experience either a tumor refractory to therapy or an early or late relapse. Therefore, one of the continuing challenges in the care for Hodgkin's lymphomas today is to find effective modes for a second tumor control. High-dose chemotherapy followed by autologous stem cell support has proved to be the treatment of choice when disseminated tumors recur after primary chemo- and or radiotherapy. Nodal relapses respond well to local radiation when they recur outfield of primary radiation without B-symptoms and in stages I-II at relapse. Allogeneic stem cell support needs further intensive evaluation in controlled studies to become an established alternative. |
Duggan, D. B.Petroni, G. R.Johnson, J. L.Glick, J. H.Fisher, R. I.Connors, J. M.Canellos, G. P.Peterson, B. A.
Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial
| Veröffentlicht: |
2003, J Clin Oncol, 21, 607-14 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12586796 |
| Abstract: |
PURPOSE: In a series of trials, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) have been identified as effective treatments for Hodgkin's disease. We compared these regimens as initial chemotherapy for Hodgkin's disease. PATIENTS AND METHODS: Adult patients (N = 856) with advanced Hodgkin's disease were randomly assigned to treatment with ABVD or MOPP/ABV. The major end points were failure-free and overall survival, life-threatening acute toxicities, and serious long-term toxicities, including cardiomyopathy, pulmonary toxicity, myelodysplastic syndromes (MDS), and secondary malignancies. RESULTS: The rates of complete remission (76% v 80%, P =.16), failure-free survival at 5 years (63% v 66%, P =.42), and overall survival at 5 years (82% v 81%, P =.82) were similar for ABVD and MOPP/ABV, respectively. Clinically significant acute pulmonary and hematologic toxicity were more common with MOPP/ABV (P =.060 and.001, respectively). There was no difference in cardiac toxicity. There were 24 deaths attributed to initial treatment: nine with ABVD and 15 with MOPP/ABV (P =.057). There have been 18 second malignancies associated with ABVD and 28 associated with MOPP/ABV (P =.13). Thirteen patients have developed MDS or acute leukemia: 11 were initially treated with MOPP/ABV, and two were initially treated with ABVD but subsequently received MOPP-containing regimens and radiotherapy before developing leukemia (P =.011). CONCLUSION: ABVD and the MOPP/ABV hybrid are effective therapies for Hodgkin's disease. MOPP/ABV is associated with a greater incidence of acute toxicity, MDS, and leukemia. ABVD should be considered the standard regimen for treatment of advanced Hodgkin's disease. |
Ekstrand, B. C.Lucas, J. B.Horwitz, S. M.Fan, Z.Breslin, S.Hoppe, R. T.Natkunam, Y.Bartlett, N. L.Horning, S. J.
Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial
| Veröffentlicht: |
2003, Blood, 101, 4285-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12586628 |
| Abstract: |
Lymphocyte-predominant Hodgkin disease (LPHD) is a unique clinical entity characterized by indolent nodal disease that tends to relapse after standard radiotherapy or chemotherapy. The malignant cells of LPHD are CD20+ and therefore rituximab may have activity with fewer late effects than standard therapy. In this phase 2 trial, 22 patients with CD20+ LPHD received 4 weekly doses of rituximab at 375 mg/m2. Ten patients had previously been treated for Hodgkin disease, while 12 patients had untreated disease. All 22 patients responded to rituximab (overall response rate, 100%) with complete response (CR) in 9 (41%), unconfirmed complete response in 1 (5%), and partial response in 12 (54%). Acute treatment-related adverse events were minimal. With a median follow-up of 13 months, 9 patients had relapsed, and estimated median freedom from progression was 10.2 months. Progressive disease was biopsied in 5 patients: 3 had recurrent LPHD, while 2 patients had transformation to large-cell non-Hodgkin lymphoma (LCL). All 3 patients with recurrent LPHD were retreated with rituximab, with a second CR seen in 1 patient and stable disease in 2. Rituximab induced prompt tumor reduction in each of 22 LPHD patients with minimal acute toxicity; however, based on the relatively short response duration seen in our trial and the concerns about transformation, rituximab should be considered investigational treatment for LPHD. Further clinical trials are warranted to determine the optimal dosing schedule of rituximab, the potential for combination treatment, and the possible relationship of rituximab treatment to the development of LCL. |
Engert, A.Schiller, P.Josting, A.Herrmann, R.Koch, P.Sieber, M.Boissevain, F.De Wit, M.Mezger, J.Duhmke, E.Willich, N.Muller, R. P.Schmidt, B. F.Renner, H.Muller-Hermelink, H. K.Pfistner, B.Wolf, J.Hasenclever, D.Loffler, M.Diehl, V.
Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
2003, J Clin Oncol, 21, 3601-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12913100 |
| Abstract: |
PURPOSE: To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy. PATIENTS AND METHODS: Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). RESULTS: Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm. CONCLUSION: Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD. |
Federico, M.Bellei, M.Brice, P.Brugiatelli, M.Nagler, A.Gisselbrecht, C.Moretti, L.Colombat, P.Luminari, S.Fabbiano, F.Di Renzo, N.Goldstone, A.Carella, A. M.
High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy
| Veröffentlicht: |
2003, J Clin Oncol, 21, 2320-5 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12805333 |
| Abstract: |
PURPOSE: To determine whether high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT) should be included in the initial consolidative treatment of patients with advanced, unfavorable Hodgkin's lymphoma (HL). PATIENTS AND METHODS: One hundred sixty-three patients achieving complete remission (CR) or partial remission (PR) with four initial courses of doxorubicin, bleomycin, vinblastine, and dacarbazine, or other doxorubicin-containing regimens, were randomly assigned to receive HDT plus ASCT (83 patients) versus four courses of conventional chemotherapy (80 patients). Unfavorable HL was defined as the presence of at least two of the following poor prognostic factors: high lactate dehydrogenase level, large mediastinal mass (greater than at least 33% of the thoracic diameter), more than one extranodal site, low hematocrit level, and inguinal involvement. RESULTS: At the end of the treatment program, 92% of patients in arm A and 89% in arm B achieved a CR (P =.6). After a median follow-up of 48 months, the 5-year failure-free survival rates were 75% (95% confidence interval [CI], 65 to 85) in arm A and 82% (95% CI, 73 to 90) in arm B (P =.4). The 5-year overall survival rates were 88% (95% CI, 80 to 96) in arm A and 88% (95% CI, 79 to 96) in arm B (P =.99). The 5-year relapse-free survival rates were 88% in arm A (95% CI, 80 to 96) and 94% in arm B (95% CI, 88 to 100), and the difference was not significant (P =.3). CONCLUSION: Patients with advanced unfavorable HL achieving CR or PR after four courses of doxorubicin-containing regimens have a favorable outcome with conventional chemotherapy. No benefit from an early intensification with HDT and ASCT was shown. |
Glossmann, J. P.Engert, A.Wassmer, G.Flechtner, H.Ko, Y.Rudolph, C.Metzner, B.Dorken, B.Wiedenmann, S.Diehl, V.Josting, A.
Recombinant human erythropoietin, epoetin beta, in patients with relapsed lymphoma treated with aggressive sequential salvage chemotherapy--results of a randomized trial
| Veröffentlicht: |
2003, , 82, 469-75 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12910374 |
| Abstract: |
The aim of the study was to investigate the effects of erythropoietin (epoetin beta) on red blood cell (RBC) transfusions, hemoglobin (Hb) levels, and quality of life (QOL) in patients with relapsed lymphoma treated with an aggressive sequential salvage chemotherapy (SSCT) regimen. Sixty patients with early or late relapsed Hodgkin's disease ( n=39) or first relapse of aggressive non-Hodgkin's lymphoma ( n=21) were randomized to receive epoetin beta 10,000 IE subcutaneously three times a week or no epoetin during salvage chemotherapy. Patients in both study arms received two cycles of DHAP (dexamethasone, high-dose cytarabine, cisplatin); patients in partial remission (PR) or complete remission (CR) then received cyclophosphamide, followed by peripheral blood stem cell (PBSC) harvest, methotrexate plus vincristine, and etoposide. The final myeloablative course was BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by autologous stem cell support. The primary endpoint of the study was the number of RBC units needed during SSCT. In addition, Hb levels and QOL were measured. The mean number of RBC units given in the epoetin beta arm was 4.5 compared to 8.3 in the control arm ( P=0.0134). The mean Hb levels during therapy were 10.4 g/dl in the epoetin beta arm and 9.7 g/dl in the control ( P=0.018). From baseline until BEAM therapy QOL (EORTC QLQ C30) and fatigue (MFI) assessment showed little QOL worsening or stable levels in both arms with a steeper increase of fatigue levels in the control group. Patients with relapsed lymphoma undergoing aggressive chemotherapy and stem cell support benefited from epoetin beta therapy, with a decrease of RBC transfusion requirements and lower rise of fatigue levels. |
Huang, J. Z.Weisenburger, D. D.Vose, J. M.Greiner, T. C.Aoun, P.Chan, W. C.Lynch, J. C.Bierman, P. J.Armitage, J. O.
Diffuse large B-cell lymphoma arising in nodular lymphocyte predominant hodgkin lymphoma. A report of 21 cases from the Nebraska Lymphoma Study Group
| Veröffentlicht: |
2003, Leuk Lymphoma, 44, 1903-10 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14738141 |
| Abstract: |
We sought to investigate the clinical characteristics and pathologic features and survival outcome of patients with diffuse large B-cell lymphoma (DLBCL) arising in nodular lymphocyte predominant Hodgkin's disease (NLPHL), since controversy regarding their prognosis exists in the literature. Twenty-one patients with DLBCL arising either concurrently with (n = 7) or subsequent to (n = 14) a diagnosis of NLPHL were identified in the Nebraska Lymphoma Study Group Registry. The clinical and pathologic features of the cases were evaluated, and survival analysis was performed from the time of diagnosis of DLBCL. The median time to the development of DLBCL in those with prior NLPHL was only one year (range, 0.5-24 years). The median age of the patients at the time of diagnosis of DLBCL was 46 years (range, 18-72 years) and the male to female ratio was 17:4. Ten patients presented with nodal DLBCL only, six patients presented with both nodal and extranodal involvement, and five patients presented with only extranodal DLBCL. Eleven patients had limited stage (I/II) disease and 10 had advanced stage (III/IV) disease. The median overall survival (OS) and failure-free survival (FFS) of the entire group was 35 months and 11 months, respectively, and the predicted five-year OS and FFS was 31 and 18%, respectively. There were no significant differences in the survival outcomes between patients with DLBCL arising in NLPHL and age- and sex- matched patients with de novo DLBCL. In conclusion, our findings suggest that patients with DLBCL arising in NLPHL have a prognosis similar to those with de novo DLBCL and should be treated aggressively. |
Josting, A.Wiedenmann, S.Franklin, J.May, M.Sieber, M.Wolf, J.Engert, A.Diehl, V.
Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: a report from the German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
2003, J Clin Oncol, 21, 3440-6 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12668650 |
| Abstract: |
PURPOSE: To assess the incidence and outcome of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients with Hodgkin's disease (HD). PATIENTS AND METHODS: Between 1981 and 1998, the GHSG conducted three trial generations for early, intermediate, and advanced HD involving a total of 5,411 patients (called HD1 through HD9). RESULTS: A total of 46 patients with secondary AML/MDS were identified. The median age at diagnosis of leukemia was 47 years (range, 22 to 79 years). Primary therapy was as follows: radiotherapy alone (n = 4); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; n = 1); cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/ABVD or similar (n = 30); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) baseline (n = 2); and BEACOPP escalated (n = 9). Twelve patients developed AML/MDS after salvage therapy, including four patients who developed AML/MDS after high-dose chemotherapy with autologous stem-cell transplantation. Thirty-six of the secondary malignancies were AML, and 10 malignancies were MDS. After a median observation time of 55 months, incidence of secondary AML/MDS was 1%. Treatment for secondary AML/MDS was as follows: cytarabine (Ara-C)-containing regimens (6-thioguanin, cytarabine, daunorubicin [TAD]/high-dose cytarabine, mitoxantrone [HAM], HAM, Ida-Ara-C (idarubicin + Ara-C), Ida-Flag (idarubicin, fludarabin, Ara-C, G-CSF), and idarubicin, cytarabine, etoposide [ICE]+HAM; n = 11), TAD-chemotherapy (n = 5), other regimens (n = 3), no treatment or supportive care (n = 24), palliative oral chemotherapy (n = 3), and allogeneic stem cell transplantation (n = 9). After 24 months of observation, no difference in freedom from treatment failure and overall survival (2% and 8%, respectively) was observed in patients who developed AML or MDS. CONCLUSION: The prognosis of patients with secondary AML/MDS after primary HD is poor. Thus, emphasis should be made to improve initial treatment in an attempt to prevent this complication. |
Murphy, S. B.Morgan, E. R.Katzenstein, H. M.Kletzel, M.
Results of little or no treatment for lymphocyte-predominant Hodgkin disease in children and adolescents
| Veröffentlicht: |
2003, J Pediatr Hematol Oncol, 25, 684-7 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12972802 |
| Abstract: |
PURPOSE: The nodular lymphocyte-predominant form of Hodgkin disease (LPHD) is a distinct clinicopathologic entity with a favorable prognosis. To see if children and adolescents could be spared the adverse sequelae of treatment, the authors adopted a policy of little or no treatment of localized LPHD in 1989. PATIENTS AND METHODS: Presentation, pathology, and outcomes were reviewed for 15 consecutive children and adolescents with LPHD seen at a single institution since 1989. One patient was lost to follow-up and two patients were seen only once in consultation and treated elsewhere. These three cases were excluded, leaving twelve: nine males and three females, ranging in age at diagnosis from 2 to 17 years (median 11). Eleven of the 12 had stage I disease, and 1 had stage II. Six received no treatment following excisional biopsy, while five received a brief treatment with chemotherapy only. One was initially treated with involved field radiotherapy (IFRT) due to an initially imprecise histologic diagnosis of classic Hodgkin disease. RESULTS: All patients are alive, without evidence of disease, for periods ranging from 2 to 13+ years after diagnosis (median 6 years). One patient recurred locally with LPHD 6 years after initial brief chemotherapy and was then treated with IFRT, achieving a prolonged second remission. CONCLUSION: Children and adolescents with localized LPHD have an excellent prognosis and may be safely approached either with a wait-and-see attitude of no initial therapy after initial adenectomy or with less aggressive treatments. |
Pellegrino, B.Terrier-Lacombe, M. J.Oberlin, O.Leblanc, T.Perel, Y.Bertrand, Y.Beard, C.Edan, C.Schmitt, C.Plantaz, D.Pacquement, H.Vannier, J. P.Lambilliote, C.Couillault, G.Babin-Boilletot, A.Thuret, I.Demeocq, F.Leverger, G.Delsol, G.Landman-Parker, J.
Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology
| Veröffentlicht: |
2003, J Clin Oncol, 21, 2948-52 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12885814 |
| Abstract: |
PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival. |
Peniket, A. J.Ruiz de Elvira, M. C.Taghipour, G.Cordonnier, C.Gluckman, E.de Witte, T.Santini, G.Blaise, D.Greinix, H.Ferrant, A.Cornelissen, J.Schmitz, N.Goldstone, A. H.
An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation
| Veröffentlicht: |
2003, Bone Marrow Transplant, 31, 667-78 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12692607 |
| Abstract: |
The role of allogeneic bone marrow transplantation in lymphoma remains uncertain. We have analyzed 1185 allogeneic transplants for lymphoma reported to the EBMT registry between 1982 and 1998 and compared the results with those of 14687 autologous procedures performed over the same period. Patients receiving allogeneic transplants were subdivided according to histology: low-grade non-Hodgkin's lymphoma (NHL) 231 patients; intermediate-grade NHL 147 patients; high-grade NHL 255 patients; lymphoblastic NHL 314 patients; Burkitt's lymphoma 71 patients; and Hodgkin's disease 167 patients. These patients received allogeneic transplants as their first transplant procedure. Actuarial overall survival (OS) at 4 years from transplantation was: low-grade NHL 51.1%; intermediate-grade NHL 38.3%; high-grade NHL 41.2%; lymphoblastic lymphoma 42.0% years; Burkitt's lymphoma 37.1%; and Hodgkin's disease 24.7% years. These outcomes are relatively poor because of the high procedure-related mortality associated with these procedures, particularly in patients with Hodgkin's disease (51.7% actuarial procedure-related mortality at 4 years). Multivariate analysis showed that for all lymphomas apart from Hodgkin's disease, status at transplantation significantly affected outcome. A matched analysis was performed: for all categories of lymphoma, OS was better for autologous than for allogeneic transplantation. Relapse rate was better in the allogeneic group for low-, intermediate- and high-grade, and lymphoblastic NHL. It was equivalent for Burkitt's lymphoma and worse in the allogeneic group for Hodgkin's disease. Allogeneic transplantation appears to be superior to autologous procedures in terms of producing a lower relapse rate. The toxicity of allogeneic procedures must however be reduced before this translates into an improvement in OS. |
Rehwald, U.Schulz, H.Reiser, M.Sieber, M.Staak, J. O.Morschhauser, F.Driessen, C.Rudiger, T.Muller-Hermelink, K.Diehl, V.Engert, A.
Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group
| Veröffentlicht: |
2003, Blood, 101, 420-4 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12509381 |
| Abstract: |
This phase 2 trial was performed to evaluate the safety and efficacy of the chimeric monoclonal anti-CD20 antibody rituximab in patients with relapsed lymphocyte-predominant Hodgkin lymphoma or other CD20(+) subtypes of Hodgkin disease (HD). Eligibility criteria required expression of the CD20 antigen on more than 30% of malignant cells. Fourteen patients were treated with 4 weekly intravenous infusions of rituximab (375 mg/m(2)). All patients had at least one prior chemotherapy (median, 2). The median time from first diagnosis was 9 years. Adverse events, such as rhinitis, fever, chills, and nausea, were usually transient and of mild to moderate grade, allowing outpatient treatment in most cases. All patients completed treatment and were eligible for a response. The overall response in 14 assessable patients was 86%, with 8 complete remissions and 4 partial remissions, and 2 patients with progressive disease. At a median follow-up of 12 months, 9 of 12 responders were in remission. The median duration of response has not been reached yet (20+ months). We conclude that rituximab is both safe and effective in a subgroup of CD20(+) patients with HD. |
Sieber, M.Bredenfeld, H.Josting, A.Reineke, T.Rueffer, U.Koch, T.Naumann, R.Boissevain, F.Koch, P.Worst, P.Soekler, M.Eich, H.Muller-Hermelink, H. K.Franklin, J.Paulus, U.Wolf, J.Engert, A.Diehl, V.
14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced-stage Hodgkin's lymphoma: results of a pilot study of the German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
2003, J Clin Oncol, 21, 1734-9 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin's lymphoma. PATIENTS AND METHODS: From July 1997 until March 2000, 94 patients with Hodgkin's lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. RESULTS: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin's lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. CONCLUSION: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin's Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial. |
Sureda, A.Robinson, S. P.Ruiz de Elvira, M. C.Taghipour, G.Carella, A. M.Mackinnon, S.Boogaerts, M.Caballero, M. D.Michallet, M.Russell, N.Schmitz, N.
Non Myeloablative Allogeneic Stem Cell Transplantation Significantly Reduces Transplant Related Mortality in Comparison with Conventional Allogeneic Transplantation in Relapsed or Refractory Hodgkins Disease: Results of the European Group for Blood and Marrow Transplantation
| Veröffentlicht: |
2003, Blood, 102, 692a |
| PubMedLink: |
|
| Abstract: |
Overall results with conventional allogeneic stem cell transplantation (allo-SCT) in relapsed or refractory Hodgkins disease (HD) patients are extremely poor due to a transplant related mortality (TRM) as high as 50% in some series. The use of a non myeloablative transplant protocol (NMT) could improve long-term survival by reducing TRM. We have analysed the outcome in terms of overall survival (OS), progression free survival (PFS), TRM and relapse rate (RR) in patients with relapsed or refractory HD treated with a NMT (n = 99) or a conventional allo-SCT (n = 154) between January/1997 and July/2001 and reported to the EBMT lymphoma database. Patients with 2 allo-SCT or 2 prior autologous stem cell transplantations (ASCT) had been previously excluded from the analysis. Age at diagnosis and at allo-SCT, disease characteristics at diagnosis, stem cell source, conditioning regimen and disease status before ASCT and disease status at allo-SCT were similar in both groups. A previous ASCT was more frequent in the NMT group (55% vs 37%, p = 0.004) as well as the use of peripheral blood (88% vs 62% p = 0.0001) and a CMV positive donor at transplantation (63% vs 38%, p = 0.013). TBI-containing regimens were more frequent in the conventional group (11% vs 30%, p = 0.002) as well as the use of cytokines after transplantation (33% vs 52%, p = 0.05). The complete remission rate as well as the incidence of acute graft versus host disease were similar in both groups (42% vs 54% and 44% vs 56%, respectively). The use of a conventional regimen [relative risk (RR) 1.7 (95% CI 1.02 2.82), p = 0.03], resistant disease before allo-SCT [RR 1.68 (95% CI 1.08 2.62), p = 0.02] and a prior ASCT [RR 1.8 (95% CI 1.15 2.85), p = 0.01] were unfavourable prognostic factors for OS. Resistant disease at allo-SCT significantly reduced the PFS [RR 1.96 (95% CI 1.31 2.93), p = 0.0011] probably by increasing the RR after the procedure [RR 2.04 (95% CI 1.12 3.71), p = 0.02] and a prior ASCT [RR 2.34 (95% CI 1.29 4.24), p = 0.005], a conventional allo-SCT [RR 2.61 (95% CI 1.26 5.39), p = 0.01] and resistant disease [RR 2.43 (95% CI 1.30 4.48), p = 0.005] significantly increased the TRM. The use of a NMT is associated with a lower TRM and an improved survival when compared with conventional allo-SCT in refractory or relapsed HD patients. Disease status before allo-SCT is the major prognostic factor for predicting outcome after allo-SCT and disease relapse remains a significant problem in this setting with a relapse rate around 50% at 4 years with both regimens. |
van Leeuwen, F. E.Klokman, W. J.Stovall, M.Dahler, E. C.van't Veer, M. B.Noordijk, E. M.Crommelin, M. A.Aleman, B. M.Broeks, A.Gospodarowicz, M.Travis, L. B.Russell, N. S.
Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin's disease
| Veröffentlicht: |
2003, J Natl Cancer Inst, 95, 971-80 |
| PubMedLink: |
|
| Abstract: |
BACKGROUND: Female survivors of Hodgkin's disease (HD) have a strongly elevated risk of breast cancer, but factors responsible for the increased risk are not well known. METHODS: We investigated the effects of radiation dose, chemotherapy (CT), and reproductive factors on breast cancer risk in a nested case-control study in The Netherlands in a cohort of 770 female patients who had been diagnosed with HD before age 41. Detailed treatment information and data on reproductive factors were collected for 48 case patients who developed breast cancer 5 or more years after diagnosis of HD and 175 matched control subjects. The radiation dose was estimated to the area of the breast where the case patient's tumor had developed and to a comparable location in matched control subjects. Relative risks (RRs) of breast cancer were calculated by conditional logistic regression. Statistical tests were two-sided. RESULTS: The risk of breast cancer increased statistically significantly with radiation dose (P(trend) =.01); patients who received 38.5 Gy or more had an RR of 4.5 (95% confidence interval [CI] = 1.3 to 16) times that of patients who received less than 4 Gy. Patients who received both CT and radiotherapy (RT) had a statistically significantly lower risk than those treated with RT alone (RR = 0.45, 95% CI = 0.22 to 0.91). Breast cancer risk increased with increasing radiation dose among patients who received RT only (RR = 12.7, 95% CI = 1.8 to 86, for patients receiving > or =38.5 Gy) but not among patients treated with CT and RT. Sixty-nine percent of control subjects treated with RT and more than six cycles of CT, but only 9% of those who received RT alone, reached menopause before age 41. Reaching menopause before age 36 was associated with a strongly reduced risk of breast cancer (RR = 0.06, 95% CI = 0.01 to 0.45). CONCLUSION: Breast cancer risk increases with increasing radiation dose up to at least 40 Gy. The substantial risk reduction associated with CT may reflect its effect on menopausal age, suggesting that ovarian hormones promote tumorigenesis after radiation has produced an initiating event. |
Witzig, T. E.White, C. A.Gordon, L. I.Wiseman, G. A.Emmanouilides, C.Murray, J. L.Lister, J.Multani, P. S.
Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-hodgkin's lymphoma
| Veröffentlicht: |
2003, J Clin Oncol, 21, 1263-70 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: Radioimmunotherapy (RIT) with yttrium-90 ((90)Y)-labeled anti-CD20 antibody ((90)Y ibritumomab tiuxetan; Zevalin, IDEC Pharmaceuticals Corporation, San Diego, CA) has a high rate of tumor response in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). This study presents the safety data from 349 patients in five studies of outpatient treatment with (90)Y ibritumomab tiuxetan. PATIENTS AND METHODS: Patients received rituximab 250 mg/m(2) on days 1 and 8, and either 0.4 mCi/kg (15 MBq/kg) or 0.3 mCi/kg (11 MBq/kg) of (90)Y ibritumomab tiuxetan on day 8 (maximum dose, 32 mCi). Patients were observed for up to 4 years after therapy or until progressive disease. RESULTS: Infusion-related toxicities were typically grade 1 or 2 and were associated with rituximab. No significant organ toxicity was noted. Toxicity was primarily hematologic, with nadir counts occurring at 7 to 9 weeks and lasting approximately 1 to 4 weeks depending on the method of calculation. After the 0.4-mCi/kg dose, grade 4 neutropenia, thrombocytopenia, and anemia occurred in 30%, 10%, and 3% of patients, respectively, and after the 0.3-mCi/kg dose, these grade 4 toxicities occurred in 35%, 14%, and 8% of patients, respectively. The risk of hematologic toxicity increased with degree of baseline bone marrow involvement with NHL. Seven percent of patients were hospitalized with infection (3% with neutropenia) and 2% had grade 3 or 4 bleeding events. Myelodysplasia or acute myelogenous leukemia was reported in five patients (1%) 8 to 34 months after treatment. CONCLUSION: Single-dose (90)Y ibritumomab tiuxetan RIT has an acceptable safety profile in relapsed NHL patients with less than 25% lymphoma marrow involvement, adequate marrow reserve, platelets greater than 100,000 cells/ micro L, and neutrophils greater than 1,500 cells/ micro L. |
Younes, A.Romaguera, J.Hagemeister, F.McLaughlin, P.Rodriguez, M. A.Fiumara, P.Goy, A.Jeha, S.Manning, J. T., Jr.Jones, D.Abruzzo, L. V.Medeiros, L. J.
A pilot study of rituximab in patients with recurrent, classic Hodgkin disease
| Veröffentlicht: |
2003, Cancer, 98, 310-4 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12872350 |
| Abstract: |
BACKGROUND: To explore the potential role of infiltrating benign B cells in classic Hodgkin disease (HD) lesions in supporting the survival of malignant Hodgkin and Reed-Sternberg (H/RS) cells, the authors initiated a pilot study of rituximab. Rituximab is used to primarily deplete normal B cells from HD lesions. METHODS: Patients with recurrent, classic HD who had received a minimum of two prior treatment regimens, regardless of whether H/RS cells expressed CD20, were treated with 6 weekly doses of 375 mg/m2 rituximab to selectively deplete infiltrating benign B cells. Objective tumor response was determined 3 weeks after completion of the last dose of rituximab and every 3 months thereafter. Serum samples were collected from patients before they started rituximab therapy and 3 weeks after the final course of rituximab. Serum cytokine levels of interleukin 6 (IL-6), IL-10, IL-12, IL-13, and interferon gamma were determined using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Twenty-two patients with nodular sclerosis histology were evaluable for treatment response. Five patients (22%) achieved partial or complete remission that lasted for a median of 7.8 months (range, 3.3-14.9 months). Remissions were observed in patients only at lymph node and splenic sites, but not at extranodal sites, and were irrespective of CD20 expression by H/RS cells. Furthermore, systemic (B) symptoms resolved in six of seven patients after therapy. In two patients, partial remissions were associated with a decline in serum IL-6 levels. CONCLUSIONS: The current data suggest that rituximab therapy in patients with recurrent, classic HD can alter serum IL-6 cytokine levels, can improve B symptoms, and may result in clinical remissions. |
2004
Ansell, S. m.Byrd, J. C.Horwitz, S. M.Borchmann, P.Engert, A.Strair, R.Khan, K. D.Fischkoff, S. A.Yellin, M.
Phase I/II, Open-Label, Dose-Escalating Study of MDX-060 Administered Weekly for 4 Weeks in Subjects with Refractory/Relapsed CD30 Positive Lymphoma.
| Veröffentlicht: |
2004, Blood, 104, 2636a |
| PubMedLink: |
|
| Abstract: |
Background: MDX-060 is a fully human anti-CD30 IgG1k monoclonal antibody that induces Fc-receptor mediated killing of CD30 expressing cell lines and inhibits the growth of CD30-expressing tumor cells in a murine xenograft model. We previously reported data from the first 31 patients in a Phase I/II open-label, dose escalation study of MDX-060 in patients with relapsed or refractory CD30+ lymphomas. The purpose of the study is to determine the safety and tolerability profile of the drug, and to preliminarily evaluate efficacy. We now update the findings of this study, including reporting the results of a new higher dose cohort. Methods: In the Phase I portion of the study, MDX-060 was administered intravenously at dose levels of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of 3-6 patients. In the Phase II portion of the study additional patients were administered MDX-060 intravenously at 10 (n=10) or 15 (n=17) mg/kg weekly for 4 weeks. Responses were assessed at month 2. Results: To date, MDX-060 has been administered to 48 patients; 40 with Hodgkin's disease (HD), 6 with anaplastic large cell lymphoma (ALCL) and 2 with other CD30 positive lymphomas. MDX-060 has been well tolerated, and a maximum tolerated dose has not been identified. There were 2 drug-related serious adverse events, 1 patient in the 1 mg/kg dosing cohort had Grade 3 elevated liver transaminase, and 1 patient in the 15 mg/kg cohort had Grade 3 pneumonia/Grade 4 ARDS. Objective clinical responses have been observed in 5 patients. Two patients had complete responses; 1 patient with ALCL in the 1 mg/kg cohort lasting 100 days, and 1 patient with HD in the 15 mg/kg cohort lasting 117 days. Retreatment of the ALCL patient with MDX-060 resulted in a second complete response. Three patients had partial responses; 1 patient with HD in the 5 mg/kg cohort lasting 92 days, and 1 patient with HD in the 15 mg/kg cohort, which is continuing at 176 days. In addition, 1 patient with ALCL in the 15 mg/kg cohort had a partial response. Stable disease was observed in 17 patients following MDX-060 administration with a median duration of 132 days (range:15-387 days). Baseline soluble CD30 levels in the plasma were evaluated, but did not appear to correlate with clinical outcome. Conclusions: Preliminary evidence indicates MDX-060 to be well tolerated in heavily pre-treated patients with CD30+ lymphomas, with minimal toxicity, and with clinical activity observed at 1 mg/kg, 5 mg/kg and 15 mg/kg. Additional patients are being accrued at 1 mg/kg and 5 mg/kg to more accurately assess efficacy at these dose levels. |
Bonadonna, G.Bonfante, V.Viviani, S.Di Russo, A.Villani, F.Valagussa, P.
ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results
| Veröffentlicht: |
2004, J Clin Oncol, 22, 2835-41 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15199092 |
| Abstract: |
PURPOSE: Radiation therapy (RT) alone can cure more than 80% of all patients with pathologic stage IA, IB, and IIA Hodgkin's disease, but some prognostic factors unfavorably affect treatment outcome. Combined-modality approaches improved results compared with RT, but the optimal extent of RT fields when combined with chemotherapy warranted additional evaluation. PATIENTS AND METHODS: In February 1990, we activated a prospective trial in patients with early, clinically staged Hodgkin's disease to assess efficacy and tolerability of four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by either subtotal nodal plus spleen irradiation (STNI) or involved-field radiotherapy (IFRT). RESULTS: Main patient characteristics were fairly well balanced between the two arms. Complete remission was achieved in 100% and in 97% of patients, respectively. The 12-year freedom from progression rates were 93% (95% CI, 83% to 100%) after ABVD and STNI, and 94% (95% CI, 88% to 100%) after ABVD and IFRT, whereas the figures for overall survival were 96% (95% CI, 91% to 100%) and 94% (95% CI, 89% to 100%), respectively. Apart from three patients who developed second malignancies in the STNI arm, treatment-related morbidities were mild. CONCLUSION: Present long-term findings suggest that, after four cycles of ABVD, IFRT can achieve a worthwhile outcome. The limited size of our patient sample, however, had no adequate statistical power to test for noninferiority of IFRT versus STNI. Despite this, ABVD followed by IFRT can be considered an effective and safe modality in early Hodgkin's disease with both favorable and unfavorable presentation. |
Bredenfeld, H.Franklin, J.Nogova, L.Josting, A.Fries, S.Mailander, V.Oertel, J.Diehl, V.Engert, A.
Severe pulmonary toxicity in patients with advanced-stage Hodgkin's disease treated with a modified bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine (BEACOPP) regimen is probably related to the combination of gemcitabine and bleomycin: a report of the German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
2004, J Clin Oncol, 22, 2424-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15136597 |
| Abstract: |
PURPOSE: To investigate a new effective, nonleukemogenic polychemotherapy regimen, BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine) in a phase I/II dose-escalation study in patients with advanced-stage Hodgkin' s disease (HD). PATIENTS AND METHODS: Patients in clinical stages IIB with risk factors III and IV were enrolled in this nonrandomized, multicenter trial aimed at defining the maximum-tolerated dose of gemcitabine within a modified escalated BEACOPP regimen. Gemcitabine was given at a starting dose of 800 mg/m(2) on days 1 and 4 of each cycle. RESULTS: Twenty-seven patients (eight female, 19 male) were enrolled with a median age of 33 years (range, 19 to 65 years). Due to a higher than expected hematotoxicity, the day-4 application of gemcitabine was omitted after 14 patients were included and 59 cycles were given. A total of eight patients developed lung toxicity, mainly pneumonitis (six of eight), which led to the termination of the study. With a median follow-up of 27 months, 25 patients are in continuing complete remission. CONCLUSION: The substitution of etoposide by gemcitabine in the escalated BEACOPP schema is not feasible and leads to severe pulmonary toxicity. This toxicity is probably related to the concomittant application of gemcitabine and bleomycin. |
Corradini, P.Dodero, A.Bregni, M.Olivieri, A.Farina, L.Rizzo, E.Milani, R.Scime, R.Rambaldi, A.Bonifazi, F.Patriarca, F.Locasciulli, A.Bacigalupo, A.Gianni, A. M.Tarella, C.
Reduced-Intensity Conditioning Followed by Allogeneic Stem Cell Transplantation (allo-SCT) Is an Effective Salvage Treatment for Peripheral T-Cell Non-Hodgkin’s Lymphoma (PTCL).
| Veröffentlicht: |
2004, Blood, 104, 808a |
| PubMedLink: |
|
| Abstract: |
Patients with relapsed PTCL have a poor prognosis. We had previously shown the existence of a graft-versus-lymphoma effect against PTCL (J Clin Oncol, 2004). In the present report, we extended our previous observations to 26 patients (pts) receving allo-SCT. All patients received several courses of debulkying chemotherapy (usually 3 DHAP and/or high-dose chemotherapy) followed by the same RIC regimen containing thiotepa (10 mg/kg), fludarabine (60 mg/ms) and cyclophosphamide (60 mg/kg). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. Patients’ median age was 45 years (range, 15–64). Histologic PTCL subtypes included: PTCL not otherwise specified (n=12), ALCL (n=7), angioimmunoblastic (n=3), others subtypes (n=4). Twenty-two pts (84%) received transplant from HLA-identical sibling, 3 from haploidentical sibling and one from unrelated donor. The median time from diagnosis to transplantation was 17 months. Thirteen patients (50%) had failed a previous auto and the majority received at least 2 lines of chemotherapy before allo-SCT. Seven (27%) and 13 pts (50%) were in CR and PR at the time of allo-SCT, respectively. At median follow-up of 27 months (range, 8–73), 17 (65%) were alive (n=14 in CR) and 9 died (n=6 disease, n=3 toxicity). The estimated 3-year TRM was 13%. The estimated 5 year OS and PFS projections were 61% (95% CI, 41–81%) and 51% (95% CI, 30–72%), respectively. Relapses occurred in the first 6 months after allo-SCT and we did not observe differences in PFS between specified and unspecified variants. De-novo acute GVHD (II/IV) and chronic GVHD incidence were 28% and 24%, respectively. Eight patients received DLI, 6 for relapse, 1 pre-emptive, 1 for infection: 3 responded (n=1 CR, n=2 PR). Following DLIs, 4 patients developed GVHD with associated a clinical response. In conclusion, our data indicate: 1) long-term disease control was achieved in patients with an aggressive subtype of NHL; 2) although optimal therapeutic strategies for relapsed PTCL are yet to be defined, further prospective evaluation of allo-SCT is required. |
Diehl, V.Brillant, C.Franklin, J.Hermann, R.Greil, R.Engert, A.Pfistner, B.
BEACOPP Chemotherapy for Advanced Hodgkin's Disease: Results of Further Analyses of the HD9- and HD12- Trials of the German Hodgkin Study Group (GHSG).
| Veröffentlicht: |
2004, Blood, 104, 307a |
| PubMedLink: |
|
| Abstract: |
Background: The BEACOPP regimen has proved to be superior to the conventional drug combination COPP/ABVD in the HD9 trial. In the HD12 trial, the GHSG aimed to confirm these results but at the same time attempted to reduce acute and late toxicity. Objectives: HD 9: In the recent analysis of HD9, we aim to demonstrate the benefits of BEACOPP and of dose increase after longer follow-up. In particular, we reassess the occurrence of second malignancies and the impact on OS. HD12: The HD12 trial (closed in 1/2003) aimed at de-escalating chemotherapy by comparing 8 courses of escalated BEACOPP (8 esc.BEA) with 4 escalated and 4 baseline courses of BEACOPP (4+4BEA), with or without consolidatory radiation to initial bulky and residual disease. Methods: HD9: In 1993-98, 1201 eligible patients (aged 16-65, in stages IIB and IIIA with risk factors and stages IIIB and IV) were randomised to (A) 4 double cycles COPP/ABVD, (B) 8 cycles baseline BEACOPP or (C) 8 cycles esc.BEACOPP, followed by radiation of initial bulky or residual disease. HD12: In 1999-2002, 1396 eligible patients aged 16-65 with HL in stage IIB (large mediastinal mass and/or E-lesions) or stage III-IV were randomised according to a factorial design between: (A) 8 esc.BEA + RT, (B) 8 esc.BEA no RT, (C) 4+4BEA+ RT, (D) 4+4BEA no RT. An expert panel evaluated all cases immediately after chemotherapy and, where appropriate, recommended additional radiotherapy independent of randomisation. Results: HD9: In the recent update of this trial (7/2004) with a median follow-up of 82 months, the estimated FFTF and OS rates were: arm A 67% and 79%, arm B 75% and 84%, arm C 85% and 90% (p<0.001 and p=0.004) respectively. 61 second neoplasia were documented, with similar proportions in each arm. Second AML/MDS was more frequent in arm C (11/466) than in arms B (5/469) or A (1/260). HD12: In the fourth interim analysis of HD12 (7/2004) with a median follow-up of 30 months, the FFTF rate was 88% (95%-CI: 86-90) and the OS rate 94% (92-95) for the total cohort. Radiation was given in arms A+C in 60% and in arms B+D in 9% (mostly due to panel recommendation). There were 29 secondary neoplasia, but the rate of AML/MDS (11/1396=0.8%) at this early analysis was lower than in the HD9 trial. The sequential intent-to-treat analysis demonstrated no significant differences neither between the 8 esc.BEA and 4+4BEA arms nor between the groups with or without RT. Conclusions: The results of the updated HD9 analysis convincingly demonstrate, despite an increased second leukemia rate, superior overall survival due to dose escalation of BEACOPP. Up to now the interim analysis of the HD12 trial shows no statistical difference between 8 cycles of escalated BEACOPP and 4 escalated and 4 baseline BEACOPP cycles. With a larger cohort of patients the excellent efficacy of the escalated BEACOPP regime for FFTF and OS seems to be confirmed in the HD12 trial. |
Feugier, P.Labouyrie, E.Djeridane, M.Jenabian, A.Dubruille, V.Berthou, C.Ghandour, C.Desablens, B.Chait, Y.Casassus, P.Delwail, V.Ifrah, N.Le Mevel, A.Lamy, T.Briere, J.Colonna, P.Andrieu, J. M.
Comparison of initial characteristics and long-term outcome of patients with lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma at clinical stages IA and IIA prospectively treated by brief anthracycline-based chemotherapies plus extended high-dose irradiation
| Veröffentlicht: |
2004, Blood, 104, 2675-81 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15231567 |
| Abstract: |
Lymphocyte-predominant Hodgkin lymphoma (LPHL), according to the Revised European-American Lymphoma classification, was considered on a retrospective basis as a specific clinical entity with a large majority of patients at clinical stage (CS) IA or IIA. Of the 500 patients with CS IA/IIA Hodgkin lymphoma (HL) prospectively treated between 1981 and 1996 by one or 3 courses of anthracycline-based chemotherapies combined with high-dose extended irradiation, disease in 42 patients was reclassified as LPHL. These 42 patients, none of whom had mediastinal involvement (MI), were compared with the 458 patients with classical HL (cHL), 144 without MI and 314 with MI. Surprisingly, the male-female ratio, age, first site involved, hemoglobin level, lymphocyte count, and sedimentation rate of patients with LPHL and cHL without MI were identical and significantly different from those of patients with cHL with MI. Moreover, 15-year HL mortality rates were similarly low in patients with LPHL (2.4%) and cHL without MI (0.7%). Overall survival rates were also similar (86% and 82%) and as high as 100% and 95% in patients treated before the age of 40 years. This study demonstrated that LPHL and cHL without MI shared the same presenting characteristics and the same excellent long-term prognosis after a brief anthracycline-based chemotherapy plus high-dose extended irradiation. |
Hutchings, M.Eigtved, A. I.Specht, L.
FDG-PET in the clinical management of Hodgkin lymphoma
| Veröffentlicht: |
2004, , 52, 19-32 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15363464 |
| Abstract: |
Positron emission tomography (PET) is a molecular functional imaging technique that provides qualitative and quantitative information about the localization and activity of pathophysiological processes. The most commonly used tracer for oncological purposes is 2-[18F]fluoro-2-deoxy-d-glucose (FDG). FDG-PET has within recent years become the most important nuclear medicine imaging modality in the management of lymphoma. This review summarizes the data published so far concerning the value of FDG-PET in staging, treatment monitoring, therapy planning, and follow-up of Hodgkin lymphoma (HL). FDG-PET detects more disease sites and involved organs than conventional staging procedures including computerized tomography (CT) and has a large influence on staging. FDG-PET during and after therapy appears to provide considerable prognostic information. However, the impact on patient outcome is not clear since no controlled trials are conducted and follow-up periods are generally short. The value of dual-modality PET/CT and its potential role in the radiotherapy planning is discussed. |
Josting, A.Behringer, K.Engert, A.Diehl, V.
[Modern pharmacotherapy of Hodgkin disease]
| Veröffentlicht: |
2004, Internist (Berl), 45, 93-101 |
| PubMedLink: |
|
| Abstract: |
High cure rates have been achieved in the treatment for patients with Hodgkin's disease in the past 30 years. Depending on stage at diagnosis and further risk factors up to 95% of patients with Hodgkin's disease can be cured with first-line treatment. Modern therapeutic strategies aim at both reducing therapy-induced late toxicities while maintaining effective tumor control. Patients with early stage Hodgkin's disease are now treated with a short course of chemotherapy for control of occult disease and involved field (IF) irradiation. For patients with early unfavourable stages, effectiveness of treatment shall be optimised by introducing the escalated BEACOPP schedule which has been established in the treatment of advanced stages. Questions to be answered in the treatment of advanced stages concern the optimal number of cycles of an effective chemotherapy regimen and the necessity of additional radiation therapy. The role of erythropoetin and PET-imaging is currently being evaluated in ongoing trials. In the future, new therapeutic approaches with biological agents will be of interest. |
Klimm, B.Engert, A.Diehl, V.
Axillary swelling and a reduced general condition in a middle-aged man
| Veröffentlicht: |
2004, , 1, 51-4; quiz 1 p following 54 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16264800 |
| Abstract: |
BACKGROUND: A 48-year-old man presented to his GP with an indolent swelling in his left axillary region. He also complained of a cough, a feeling of pressure in his chest, general poor health, and had increasingly suffered from night-time sweating and fever. Physical examination and an ultrasound revealed an enlarged lymph node of almost 4 cm in the left axillary region and several smaller lymph nodes of 1.5-2.0 cm in the left cervical region. Laboratory tests were unremarkable, except for an elevated erythrocyte sedimentation rate. INVESTIGATIONS: Excisional biopsy, radiography, ultrasound, CT scan, bone marrow biopsy, radionuclide imaging, echocardiography and lung function tests. DIAGNOSIS: Early-stage unfavorable (intermediate) lymphocyte-rich classical Hodgkin's lymphoma. MANAGEMENT: Chemotherapy (treatment with doxorubicin, bleomycin, vinblastine and dacarbazine) and involved-field radiotherapy. |
Loenard, J. P.Rosenblatt, J. D.Bartlett, N. L.Gopal, A.Younes, A.Fisher, D.Foss, F.Forero, A.Bernstein, S.Cheson, B.Carabasi, M. H.Bociek, R. G.Hart, B.McDonald, M.
Phase II Study of SGN-30 (Anti-CD30 Monoclonal Antibody) in Patients with Refractory or Recurrent Hodgkin's Disease.
| Veröffentlicht: |
2004, Blood, 104, 2635a |
| PubMedLink: |
|
| Abstract: |
SGN-30 is a chimeric monoclonal antibody which recognizes the CD30 antigen found on tumor cells from patients with Hodgkin’s disease (HD) and anaplastic large cell lymphoma (ALCL). Preclinical studies with this agent have demonstrated anti-lymphoma effects in both in vitro cell line assays and in vivo murine model systems. The results of a multi-dose phase I study showed minimal toxicity associated with doses from 2 to 12 mg/kg administered as six weekly IV infusions over 120 minutes each. Of the 21 patients with Hodgkin's Disease accrued to the phase I study, four patients had stable disease (SD). A phase II multi-dose study is currently underway to further evaluate the safety, antitumor activity and pharmacokinetics of six weekly IV infusions of 6 mg/kg of SGN-30 in patients with relapsed or refractory HD or systemic ALCL (sALCL). Fifteen subjects (6M, 9F) with HD have been enrolled, with baseline data as follows: median age 34 (range 20-65), median number of prior therapies 3 (range 1-5), and 11 patients (73%) have disease which progressed after prior high-dose chemotherapy and stem cell transplant. Multiple doses of SGN-30 have been well tolerated in all subjects. Drug-related adverse events have been typically mild and consistent with monoclonal antibody administration. The most common drug-related adverse event has been fatigue. No grade 3/4 events have occurred. Twelve patients are currently evaluable for response, with 6 having had stabilization of their disease. Assessment of duration of disease stabilization and response is continuing. While the acceptable safety profile and frequency of stable disease following therapy in this heavily pretreated patient population are encouraging, a 12 mg/kg/dose regimen is now being tested in subsequent subjects to further explore the dose-response relationship of SGN-30 in Hodgkin's Disease. Further evaluation of this novel immunotherapy in additional HD patients is ongoing. |
Marafioti, T.Pozzobon, M.Hansmann, M. L.Delsol, G.Pileri, S. A.Mason, D. Y.
Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease
| Veröffentlicht: |
2004, Blood, 103, 188-93 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12881301 |
| Abstract: |
The neoplastic cells in classical Hodgkin disease (Reed-Sternberg cells) are of B-lymphoid origin, but they lack many markers of this cell lineage, for example, immunoglobulin, CD20, and B-cell-associated transcription factors. In contrast, the neoplastic cells ("L&H" cells) in lymphocyte predominance Hodgkin disease retain the molecular profile of germinal center B cells. In this paper, we investigated the expression in Hodgkin disease (45 cases and 3 cell lines) of 5 intracellular signaling molecules found in B cells. The Src family kinase Syk, the B-cell adaptor protein BLNK, and phospholipase C (PLC)-gamma2 were consistently absent from Reed-Sternberg cells, whereas 2 other Src kinases (Lyn and Fyn) were heterogeneously expressed in a proportion of cases (12% and 42%, respectively). In contrast, the tumor cells in all cases of lymphocyte predominance Hodgkin disease were positive for Fyn, Syk, BLNK, and PLC-gamma2, and Lyn immunostaining was seen in a minority of biopsies. These results indicate that in Reed-Sternberg cells, the defect in B-cell lineage marker expression includes a spectrum of molecules involved in intracellular signaling, a finding in keeping with recent gene expression profiling studies. Furthermore, the clear difference in expression of signaling proteins between the 2 major subtypes of Hodgkin disease may be of diagnostic value. |
Moskowitz, C. H.Kewalramani, T.Nimer, S. D.Gonzalez, M.Zelenetz, A. D.Yahalom, J.
Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease
| Veröffentlicht: |
2004, Br J Haematol, 124, 645-52 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14871252 |
| Abstract: |
Prospective randomized studies have determined that high dose therapy and autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed Hodgkin's disease (HD); however, the role of this approach in patients with primary refractory disease has been controversial. This report is an integrated analysis of 75 consecutive patients with biopsy-confirmed primary refractory HD, who were treated with high dose chemoradiotherapy (HDT) and ASCT at the Memorial Sloan Kettering Cancer Center. The patients underwent conventional dose cytoreductive chemotherapy followed by HDT and ASCT. At a median follow-up of 10 years for surviving patients, the event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) rates were 45%, 49% and 48% respectively. Only chemosensitivity to standard-dose second-line chemotherapy (SDSC) predicted for a better survival, thus responding patients had an EFS, PFS and OS of 60%, 62% and 66%, respectively, versus 19%, 23% and 17% for patients who had a poor response to SDSC (P < 0.001). While patients with chemosensitive disease have an excellent outcome with HDT and ASCT, novel approaches are needed to cure HD patients who fail front-line and second-line chemotherapy. |
Schmitz, N.Sureda, A.Robinson, S.
Allogeneic transplantation of hematopoietic stem cells after nonmyeloablative conditioning for Hodgkin's disease: indications and results
| Veröffentlicht: |
2004, , 31, 27-32 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14970934 |
| Abstract: |
A number of treatment options are available for patients with relapsed Hodgkin's disease (HD). Radiotherapy, salvage chemotherapy, high-dose therapy (HDT) followed by autologous transplantation, and classical or nonmyeloablative conditioning followed by allogeneic transplantation can all be effective in patients with relapsed HD. Patients with early relapse after modern first-line chemotherapy, as well as patients with primary progressive disease, will be candidates for innovative approaches including nonmyelablative stem cell transplant (NST). Although initial results with NST look promising, more time and structured study of both HD and NST will be necessary to ultimately define the role of NST in this disease. |
Sieber, M.Tesch, H.Pfistner, B.Rueffer, U.Paulus, U.Munker, R.Hermann, R.Doelken, G.Koch, P.Oertel, J.Roller, S.Worst, P.Bischof, H.Glunz, A.Greil, R.von Kalle, K.Schalk, K. P.Hasenclever, D.Brosteanu, O.Duehmke, E.Georgii, A.Engert, A.Loeffler, M.Diehl, V.Mueller, R. P.Willich, N.Fischer, R.Hansmann, M. L.Stein, H.Schober, T.Koch, B.
Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial
| Veröffentlicht: |
2004, Ann Oncol, 15, 276-82 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14760122 |
| Abstract: |
BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomyci n-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD. |
Straus, D. J.Portlock, C. S.Qin, J.Myers, J.Zelenetz, A. D.Moskowitz, C.Noy, A.Goy, A.Yahalom, J.
Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease
| Veröffentlicht: |
2004, Blood, 104, 3483-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15315964 |
| Abstract: |
To determine whether combined modality therapy (CMT) is superior to chemotherapy (CT) alone, 152 untreated Hodgkin disease patients with clinical stages (CSs) IA, IB, IIA, IIB, and IIIA without bulk disease were prospectively randomized to 6 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone or 6 cycles of ABVD followed by radiation therapy (RT) (3600 cGy: involved field for 11 patients, modified extended field for the rest). Of 76 patients randomized to receive RT, 65 actually received it, and 11 did not (4 progressed, 1 had bleomycin toxicity, 6 refused). For ABVD + RT, the complete remission (CR) percentage was 94% and no major response, 6%. For ABVD alone, 94% achieved a CR; 1.5%, a partial response (PR); and 4.5%, no major response. At 60 months CR duration, freedom from progression (FFP), and overall survival (OS) for ABVD + RT versus ABVD alone are 91% versus 87% (P = .61), 86% versus 81% (P = .61), and 97% versus 90% (P = .08), respectively (log-rank). The 95% confidence intervals for CR duration, FFP, and OS differences at 5 years were -8% to 15%, -8% to 18%, and -4% to 12%, respectively. Although significant differences were not seen, it is possible that a benefit in outcome of less than 20% for CMT might be seen in a larger trial. |
Thomas, R. K.Re, D.Wolf, J.Diehl, V.
Part I: Hodgkin's lymphoma--molecular biology of Hodgkin and Reed-Sternberg cells
| Veröffentlicht: |
2004, Lancet Oncol, 5, 11-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14700604 |
| Abstract: |
Classic Hodgkin's lymphoma is characterised by Hodgkin and Reed-Sternberg cells and in most cases are derived from germinal-centre B cells. Despite progress in basic research showing the natural precursor cells of Hodgkin's lymphoma, most key questions still remain unanswered. Among these are the basic transforming events, the involvement of oncogenic viruses, the mechanisms enabling Hodgkin and Reed Sternberg cells to resist apoptosis in the germinal centre, and the molecular causes of their characteristic phenotype. Beyond the disclosure of these issues, the detection of changes in gene expression, gene mutations, and chromosomal imbalances specific of Hodgkin's lymphoma are central to recent research that may allow one a better understanding of the natural history of this type of lymphoma. |
Vassilakopoulos, T. P.Angelopoulou, M. K.Siakantaris, M. P.Kontopidou, F. N.Dimopoulou, M. N.Kokoris, S. I.Kyrtsonis, M. C.Tsaftaridis, P.Karkantaris, C.Anargyrou, K.Boutsis, D. E.Variamis, E.Michalopoulos, T.Boussiotis, V. A.Panayiotidis, P.Papavassiliou, C.Pangalis, G. A.
Combination chemotherapy plus low-dose involved-field radiotherapy for early clinical stage Hodgkin's lymphoma
| Veröffentlicht: |
2004, Int J Radiat Oncol Biol Phys, 59, 765-81 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15183480 |
| Abstract: |
PURPOSE: To present our long-term experience regarding the use of chemotherapy plus low-dose involved-field radiotherapy (IFRT) for clinical Stage I-IIA Hodgkin's lymphoma. METHODS AND MATERIALS: We analyzed the data of 368 patients. Of these, 66 received mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and 302 received doxorubicin (or epirubicin), bleomycin, vinblastine, and dacarbazine [A(E)BVD]. Patients with complete remission or very good partial remission were scheduled for low-dose IFRT (< or =3200 cGy). RESULTS: The 10-year failure-free survival (FFS) and overall survival (OS) rate was 85% and 86%, respectively. A(E)BVD-treated patients had superior 10-year FFS and OS rates compared with MOPP-treated patients (87% vs. 75%, p = 0.009; and 93% vs. 71%, p = 0.0004, respectively). Only 10 of 41 relapses had any infield (irradiated) component. Of the complete responders/very good partial responders treated with low-dose IFRT, those who received <2800 cGy had inferior FFS but similar OS as those who received 2800-3200 cGy. Adverse prognostic factors for FFS included age > or =45 years, leukocytosis > or =10 x 10(9)/L, and extranodal extension. Secondary acute leukemia developed after MOPP with or without salvage therapy (n = 6) or after ABVD plus salvage therapy (n = 2). None of the nine secondary solid tumors developed within the RT fields. CONCLUSION: IFRT at a dose of 2800-3000 cGy is highly effective in clinical Stage I-IIA HL patients who achieved a complete response or very good partial response with A(E)BVD. The long-term toxicity with respect to secondary malignancies appears to be acceptable. |
Venkatesh, H.Di Bella, N.Flynn, T. P.Vellek, M. J.Boehm, K. A.Asmar, L.
Results of a phase II multicenter trial of single-agent gemcitabine in patients with relapsed or chemotherapy-refractory Hodgkin's lymphoma
| Veröffentlicht: |
2004, Clin Lymphoma, 5, 110-5 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15453926 |
| Abstract: |
This study's objective was to determine the efficacy and safety of gemcitabine in patients with relapsed or chemotherapy-refractory Hodgkin's lymphoma (HL). Twenty-nine patients were enrolled. Eight of the first 10 patients received intravenous gemcitabine (1250 mg/m2) days 1, 8, and 15 every 4 weeks. Two patients withdrew consent before treatment. Because of toxicity, the remaining 19 patients received 1000 mg/m2 on days 1 and 8 every 3 weeks. Of the 29 treated patients, 16 (55.2%) were male, the median age was 43 years (range, 20.9-77.3), and 89.7% of them were white. Twelve patients (41.4%) had an Eastern Cooperative Oncology Group performance status (PS) of 0, 14 (48.3%) had a PS of 1, and 3 (10.3%) had a PS of 2. All patients had >/= 2 prior chemotherapy regimens. Eighteen patients (62%) had a relapse following bone marrow transplantation. Of 27 evaluable patients, 6 (22%) had partial response, 14 (52%) had stable disease, and 7 (26%) had progressive disease. The median time to progression for all patients was 6.4 months (range, 1.1-21.9). The median survival for all patients was 26.9 months (range, < 1-28.4). All patients have discontinued treatment because of disease progression or relapse. Grade >/= 3 toxicity occurred in 14 patients (48.3%): thrombocytopenia (33.3%), neutropenia (29.6%), anemia (7.4%), increased alanine aminotransferase, reduced cardiac function, and fever (3.7% for each event). This study confirms the activity of gemcitabine in relapsed and highly refractory HL. Dose and schedule may be modified in the future to optimize responses. As gemcitabine is active in highly refractory/relapsed HL, future studies should consider incorporating gemcitabine in combination regimens as first-line therapy for patients with high-risk HL. |
2005
Ballova, V.Ruffer, J. U.Haverkamp, H.Pfistner, B.Muller-Hermelink, H. K.Duhmke, E.Worst, P.Wilhelmy, M.Naumann, R.Hentrich, M.Eich, H. T.Josting, A.Loffler, M.Diehl, V.Engert, A.
A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly)
| Veröffentlicht: |
2005, Ann Oncol, 16, 124-31 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15598949 |
| Abstract: |
In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients. |
Bartlett, N. L.
Therapies for relapsed hodgkin lymphoma: transplant and non-transplant approaches including immunotherapy
| Veröffentlicht: |
2005, , , 245-51 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16304388 |
| Abstract: |
Autologous stem cell transplant remains the standard of care for relapsed Hodgkin lymphoma (HL). Approximately 50% of patients with chemo-sensitive relapse will be cured with this approach. The optimal pretransplant salvage regimen is controversial, but less toxic combinations seem to be equivalent to more aggressive approaches. For patients with chemo-refractory disease at relapse and those failing autologous transplant, the long-term prognosis remains poor. New approaches such as reduced-intensity allogeneic transplant, monoclonal antibodies targeting the CD30 antigen, Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes, and bortezomib are under investigation, but preliminary results are disappointing. New therapies are needed for patients with relapsed HL. |
Behringer, K.Breuer, K.Reineke, T.May, M.Nogova, L.Klimm, B.Schmitz, T.Wildt, L.Diehl, V.Engert, A.
Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's Lymphoma Study Group
| Veröffentlicht: |
2005, J Clin Oncol, 23, 7555-64 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16234521 |
| Abstract: |
PURPOSE: Long-term survivors of successfully treated Hodgkin's lymphoma (HL) are at risk for late complications. Among these, infertility for female patients is of major importance. The subject of this analysis is to evaluate the menstrual status after HL therapy. PATIENTS AND METHODS: From 1994 to 1998, the German Hodgkin's Lymphoma Study Group conducted clinical trials for early-, intermediate-, and advanced-stage HL (trials HD7 to HD9) involving a total of 3,186 patients. A survey was carried out to evaluate the menstrual status after therapy. The following factors were assessed concerning their influence on amenorrhea: age, treatment, stage, and the use of oral contraceptives during chemotherapy. RESULTS: A total of 405 women aged younger than 40 years answered the study questions. After a median follow-up of 3.2 years, 51.4% of the women receiving eight cycles of dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) had continuous amenorrhea. Amenorrhea was significantly more frequent after dose-escalated BEACOPP compared with doxorubicin, bleomycin, vinblastine, and dacarbazine; cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine; or standard BEACOPP (P = .0066). Amenorrhea after therapy was most pronounced in women with advanced-stage HL (P < .0001), in women older than 30 years at treatment (P = .0065), and in women who did not take oral contraceptives during chemotherapy (P = .0002). CONCLUSION: Most women who are treated for advanced-stage HL experience amenorrhea after therapy. Amenorrhea is significantly more frequent in women with advanced-stage HL receiving eight cycles of dose-escalated BEACOPP and in women older than 30 years at first treatment. Furthermore, the data show a statistical association between the use of oral contraceptives and return of menstrual cycle, which is subject to further investigation. |
Borchmann, P.Schnell, R.Engert, A.
Immunotherapy of Hodgkin's lymphoma
| Veröffentlicht: |
2005, Eur J Haematol Suppl, , 159-65 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16007886 |
| Abstract: |
Many new treatment approaches have given promising results in experimental Hodgkin's lymphoma (HL) models. Early clinical trials evaluating antibody based compounds as immunotoxins (ITs), radioimmunotherapy (RIT), bispecific molecules (BSMs), and recently monoclonal antibodies (MAbs), have demonstrated some clinical efficacy in patients with advanced refractory or relapsed HL. In addition, cellular immunotherapy is evolving. Although it seems unlikely to cure chemotherapy resistant patients with larger tumor masses by either of these approaches alone, the combination with conventional chemotherapy might help to overcome resistance of Hodgkin-/ReedSternberg (H-RS) cells. Another rationale for the development of these immunotherapies is to eliminate residual disease and thereby to prevent relapses from the disease. Currently, several clinical studies are running. A murine MAb (Ki-4) based 131 Iodine conjugate has shown efficacy in refractory HL patients in a phase II study, but less toxic constructs using alternate MAbs or isotopes should be developed. A humanized as well as a fully human anti-CD30 MAb are being tested in clinical phase I/II studies. These MAbs could engage the human immune system against the H-RS cells. In addition, these MAbs could be then combined with conventional chemotherapy in order to improve the treatment of HL. |
Cerveny, C. G.Law, C. L.McCormick, R. S.Lenox, J. S.Hamblett, K. J.Westendorf, L. E.Yamane, A. K.Petroziello, J. M.Francisco, J. A.Wahl, A. F.
Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics
| Veröffentlicht: |
2005, Leukemia, 19, 1648-55 |
| PubMedLink: |
|
| Abstract: |
SGN-30, a monoclonal antibody with activity against CD30+ malignancies, is currently in phase II clinical evaluation for treatment of Hodgkin's disease (HD) and anaplastic large cell lymphoma. The mechanisms underlying SGN-30's antitumor activity were investigated using cDNA array of L540 cells. SGN-30 treatment activated NF-kappaB and modulation of several messages including the growth regulator p21WAF1/CIP1 (p21) and cellular adhesion marker ICAM-1. p21 protein levels increased coincident with growth arrest and Annexin V/PI staining in treated HD cells. To determine if SGN-30-induced growth arrest would sensitize tumor cells to chemotherapeutics used against HD, L540cy and L428 cells were exposed to SGN-30 in combination with a panel of cytotoxic agents and resultant interactions quantified by the Combination Effects Method. Interactions between SGN-30 and all cytotoxic agents examined were additive or better. These in vitro data translated to increased efficacy of SGN-30 and bleomycin against L540cy tumor xenografts. In addition to direct cell killing, SGN-30 affects growth arrest and drug sensitization through growth regulating and proapoptotic machinery. Importantly, these data suggest that SGN-30 can enhance the efficacy of standard chemotherapies used to treat patients with CD30+ malignancies. |
Cullen, M.Steven, N.Billingham, L.Gaunt, C.Hastings, M.Simmonds, P.Stuart, N.Rea, D.Bower, M.Fernando, I.Huddart, R.Gollins, S.Stanley, A.
Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas
| Veröffentlicht: |
2005, N Engl J Med., 353, 988-98. |
| PubMedLink: |
|
| Abstract: |
BACKGROUND: The role of prophylactic antibacterial agents after chemotherapy remains controversial. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance. RESULTS: A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections. CONCLUSIONS: Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization. |
Diehl, V.Brillant, C.Engert, A.Mueller, R. P.Eich, H. T.Mueller-Hermelink, H. K.Herrmann, R.Markova, J.Ho, A.Hiddemann, W.Doerken, B.Greil, R.Josting, A.Pfistner, B.
Recent Interim Analysis of the HD11 Trial of the GHSG: Intensification of Chemotherapy and Reduction of Radiation Dose in Early Unfavorable Stage Hodgkin's Lymphoma
| Veröffentlicht: |
2005, Blood, 106, 816a |
| PubMedLink: |
|
| Abstract: |
Background: Combined modality treatment consisting of chemotherapy (CT) followed by involved field radiotherapy (IF-RT) is the standard treatment for early unfavourable Hodgkin's lymphoma (HL). Despite high complete remission (CR) rates, failures are common. We thus compared the baseline-dose BEACOPP regimen with ABVD and 20 with 30 Gy IF-RT in a prospectively randomized trial (HD11) in an attempt to improve outcome in this group of patients. Methods: Between May 1998 and January 2003, 1570 patients (pts) aged 16–75 with untreated intermediate stage HL (CS I, IIA with risk factors or IIB with elevated ESR and/or ≥ 3 nodal areas only) were randomized according to a factorial design between 4 cycles of ABVD followed by 30 Gy IF-RT (arm A - standard treatment), 4 ABVD + 20 Gy IF-RT (arm B), 4 baseline-dose BEACOPP + 30 Gy IF-RT (arm C) and 4 baseline-dose BEACOPP + 20 Gy IF-RT (arm D). Results: In the fifth preplaned interim analysis, 1293 pts were evaluable for the chemotherapy comparison and 1274 for the radiotherapy comparison. Patient characteristics were well balanced between the treatment arms. 95% of patients treated reached CR, 2% had pogressive disease, 8% relapsed and the total mortality rate was 4% with no significant differences between treatment arms for either endpoint. The most frequent haematological toxicities during chemotherapy were leucopenia observed in 32% of pts (ABVD: 25%, BEACOPP: 39%) and anemia in 4% of pts (ABVD <1%, BEACOPP 7%). Infection rate was 5% (ABVD 3%, BEACOPP 7%). The most frequent toxicity during radiotherapy was dysphagia in 5%. 14 secondary neoplasias were observed: 2 AML, 4 NHL, 8 solid tumors with no significant differences between treatment arms. After a median observation time of three years, freedom from treatment failure (FFTF) was 87% (95%-CI 85-89) and overall survival (OS) was 96% (95%-CI 95-97). Both for FFTF and OS, there was no sequential significant difference either between ABVD (FFTF 87%, OS 97%) and BEACOPP (FFTF 88%, OS 96%) nor 30 Gy (FFTF 90%, OS 97%) and 20 Gy IF-RT (FFTF 87%, OS 97%). Conclusions: At three years of median observation time, no sequential significant differences in treatment outcome were detected, neither between chemotherapy regimens nor between the different doses of radiotherapy, despite more relapses in 20 Gy radiotherapy arms. |
Diehl, V.Brillant, C.Engert, A.Mueller, R. P.Mueller-Hermelink, H. K.Hermann, R.Doerken, B.Kanz, L.Greil, R.Pfistner, B.
HD10: Investigating reduction of combined modality treatment intensity in early stage Hodgkin’s lymphoma. Interim analysis of a randomized trial of the German Hodgkin Study Group (GHSG)
| Veröffentlicht: |
2005, J Clin Oncol, 23, |
| PubMedLink: |
|
| Abstract: |
Background: Early stage Hodgkin’s lymphoma (HL) in stages I-II without risk factors currently is successfully treated with combined modality of chemotherapy (usually ABVD) followed by involved field irradiation (IF) in most study groups, reaching complete remission rates higher than 90%. In the HD10 trial the GHSG investigated if the number of ABVD cycles as well as IF-radiotherapy (RT) dose could be safely reduced. Methods: 1131 patients (pts) with early stage disease (stage I,II without risk factors) were randomized between 4 cycles vs. 2 cycles of ABVD and 30 Gy IF vs. 20 Gy IF in a 2x2 factorial design between 5/1998 and 5/2002. Primary endpoint was freedom from treatment failure (FFTF). Results: The second interim analysis conducted in August 2003 comprised of 847 pts (75%) that were well balanced between treatments arms concerning baseline characteristics. Complete remission rates were high with 98.4% of all pts while progressive disease or no change was observed in 0.9% of cases. Relapse rate was 2.5%, thirteen patients died during the study (1.5%). The most common WHO grade 3/4 toxicity during CT was leukopenia with 19% (4xABVD: 22%, 2xABVD: 15%). RT was well tolerated with dysphagia in 2.3%. So far ten secondary neoplasias were reported: 1AML, 4 NHL and 5 solid tumors. FFTF after a median observation time of two years was 96.6% with no statistical differences between CT of 4xABVD vs. 2xABVD or RT of 30Gy IF vs. 20Gy IF. Overall survival was 98.5% without any statistical differences in CT and RT comparisons either. Conclusions: Further analysis will show if these promising interim results will allow to reduce further therapy intensity in combined modality treatment of early stage HL both in terms of the composition of drugs (ABVD->AV in HD13) as well as RT dose. |
Diehl, V.Harris, N. L.Mauch, P. M.
Hodgkin´s Lymphoma: In DeVita VT, HellmannS, Rosenberg SA eds. Cancer:
| Veröffentlicht: |
2005, , , 2020-2076 |
| PubMedLink: |
|
| Abstract: |
|
Diehl, V.Klimm, B.Re, D.
Hodgkin lymphoma: a curable disease: what comes next?
Engert, A.Ballova, V.Haverkamp, H.Pfistner, B.Josting, A.Duhmke, E.Muller-Hermelink, K.Diehl, V.
Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group
| Veröffentlicht: |
2005, J Clin Oncol, 23, 5052-60 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15955904 |
| Abstract: |
PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. PATIENTS AND METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients. |
Engert, A.Pluetschow, A.Eich, H. T.Herrmann, R.Doelken, B.Kanz, L.Greil, R.Markova, J.Pfistner, B.Josting, A.Mueller-Hermelink, H. K.Mueller, R. P.Diehl, V.
Combined Modality Treatment of Two or Four Cycles of ABVD Followed by Involved Field Radiotherapy in the Treatment of Patients with Early Stage Hodgkin's Lymphoma: Update Interim Analysis of the Randomised HD10 Study of the German Hodgkin Study Group (GHSG)
| Veröffentlicht: |
2005, Blood, 106, 2673a |
| PubMedLink: |
|
| Abstract: |
Combined modality treatment is regarded as standard by most study groups for patients with early-stage Hodgkin's lymphoma (HL). However, the optimal chemotherapy, the number of cycles needed and the optimal radiotherapy dose is still unclear. The GHSG thus conducted a randomised study for patients with early stage favourable Hodgkin's lymphoma (HD10) in which these questions were addressed. A total of 1370 patients were randomised from 5/1998 to 1/2003 between two or four cycles of ABVD and independently to 20Gy or 30Gy involved field (IF) radiotherapy. For the second interim analysis at a median follow up of 28 months, 847 patients were available. Patients were equally balanced for age, gender, stage, histology, performance status and risk factors. Compared with two cycles, there was more toxicity in patients receiving four cycles of ABVD for leucopenia, hair loss and infection. Concerning radiotherapy dose, there was more toxicity associated with 30Gy for dysphagia, mucositis and leucopenia. The rate of complete remissions ranged between 98% and 99% with no significant differences among treatment arms. Freedom from treatment failure (FFTF) and overall survival showed no differences between the four treatment arms. The curves for overall survival and FFTF were nearly superimposable for all four arms. This analysis suggests that 2 chemotherapy cycles with involved field radiotherapy may be sufficient for patients with early favourable HL, but a reliable assessment must await the final analysis including all randomised patients and with adequate follow-up. The results of the third interim analysis (10/2005) including 1110 patients with a median follow up of more than 3 years will be presented. |
Gobbi, P. G.Levis, A.Chisesi, T.Broglia, C.Vitolo, U.Stelitano, C.Pavone, V.Cavanna, L.Santini, G.Merli, F.Liberati, M.Baldini, L.Deliliers, G. L.Angelucci, E.Bordonaro, R.Federico, M.
ABVD versus modified stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi
| Veröffentlicht: |
2005, J Clin Oncol, 23, 9198-207 |
| PubMedLink: |
|
| Abstract: |
PURPOSE: In this multicenter, prospective, randomized clinical trial on advanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to < or = two sites of either previous bulky or partially remitting disease (a modification of the original Stanford program). PATIENTS AND METHODS: Three hundred fifty-five patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and received six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n = 106); radiotherapy was administered to 76, 71, and 50 patients in these three arms, respectively. RESULTS: The complete response rates for ABVD, Stanford V, and MOPPEBVCAD were 89%, 76% and 94%, respectively; 5-year failure-free survival (FFS) and progression-free survival rates were 78%, 54%, 81% and 85%, 73%, and 94%, respectively (P < .01 for comparison of Stanford V with the other two regimens). Corresponding 5-year overall survival rates were 90%, 82%, and 89% for ABVD, Stanford V, and MOPPEBVCAD, respectively. Stanford V was more myelotoxic than ABVD but less myelotoxic than MOPPEBVCAD, which had larger reductions in the prescribed drug doses. CONCLUSION: When associated with conditioned and limited (not adjuvant) radiotherapy, ABVD and MOPPEBVCAD were superior to Stanford V chemotherapy in terms of response rate and FFS and progression-free survival. Patients were irradiated less often after MOPPEBVCAD, but this regimen was more toxic. ABVD is still the best choice when it is combined with optional, limited irradiation. |
Hutchings, M.Mikhaeel, N. G.Fields, P. A.Nunan, T.Timothy, A. R.
Prognostic value of interim FDG-PET after two or three cycles of chemotherapy in Hodgkin lymphoma
| Veröffentlicht: |
2005, Ann Oncol, 16, 1160-8 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15939713 |
| Abstract: |
BACKGROUND: Long-term survival from Hodgkin lymphoma (HL) is 80-90%, but the treatment has serious late adverse effects. Modern risk-adapted treatment requires accurate assessment of the patient's prognosis. This investigation assessed the value of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two or three cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: A total of 85 patients with HL underwent FDG-PET after two or three cycles of chemotherapy. Median follow-up was 3.3 years. FDG-PET results were related to PFS and OS using Kaplan-Meier analysis. Regression analyses were employed to test for independence of established pretreatment prognostic factors. RESULTS: After two or three cycles of chemotherapy, 63 patients had negative FDG-PET scans, nine patients had minimal residual uptake (MRU) and 13 patients had positive scans. Three PET-negative patients and one patient from the MRU group relapsed. In the PET-positive group, nine patients progressed and two died. Survival analyses showed highly significant associations between early interim FDG-PET and PFS (P <0.0001) and OS (P <0.03). All advanced-stage patients with positive interim FDG-PET relapsed within 2 years. CONCLUSION: Early interim FDG-PET is an accurate and independent predictor of PFS and OS in HL. A positive interim FDG-PET is highly predictive of relapse in advanced-stage disease. |
Johnson, P. W.Radford, J. A.Cullen, M. H.Sydes, M. R.Walewski, J.Jack, A. S.MacLennan, K. A.Stenning, S. P.Clawson, S.Smith, P.Ryder, D.Hancock, B. W.
Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519)
| Veröffentlicht: |
2005, J Clin Oncol, 23, 9208-18 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16314615 |
| Abstract: |
PURPOSE: To perform an open-label, randomized, controlled trial comparing treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with two multidrug regimens (MDRs) for advanced Hodgkin's lymphoma (HL). PATIENTS AND METHODS: Eight hundred seven patients with advanced HL (stage III to IV, or earlier stage with systemic symptoms or bulky disease) were randomly assigned between ABVD and MDR specified before randomization as alternating chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) with prednisolone, doxorubicin, bleomycin, vincristine, and etoposide (PABIOE), or hybrid ChlVPP/etoposide, vincristine, and doxorubicin (EVA). Radiotherapy was planned for incomplete response or initial bulk disease. RESULTS: At 52 months median follow-up, 212 event-free survival (EFS) events (disease progression or any death) were reported. In the primary comparison, at 3 years EFS was 75% (95% CI, 71% to 79%) for ABVD and 75% (95% CI, 70% to 79%) for MDRs (hazard ratio [HR] = 1.05; 95% CI, 0.8 to 1.37; HR more than 1.0 favors ABVD). The 3-year overall survival (OS) rates were 90% (95% CI, 87% to 93%) in patients allocated ABVD and 88% (95% CI, 84% to 91%) in patients allocated MDRs (HR = 1.22; 95% CI, 0.84 to 1.77). Patients receiving MDRs experienced more grade 3/4 infection, mucositis, and neuropathy. One occurrence of myelodysplastic syndrome was reported, but no acute leukemia was reported. When the two MDRs are compared separately with ABVD, neither the alternating nor the hybrid regimen showed a statistically significant difference from ABVD for EFS or OS. Subgroup analysis suggested that MDRs may be associated with poorer outcomes in older patients (heterogeneity test of OS older or younger than 45 years, P = .020). CONCLUSION: There was no evidence of significant difference in EFS or OS between ABVD and MDRs in the trial overall or if the two MDR versus ABVD comparisons are considered separately. ABVD remains the standard for treatment of advanced HL. |
Jost, L. M.Stahel, R. A.
ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of Hodgkin's disease
Josting, A.
Autologous transplantation in relapsed and refractory Hodgkin's disease
| Veröffentlicht: |
2005, Eur J Haematol Suppl, , 141-5 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16007883 |
| Abstract: |
The current data support the use of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as standard procedure for the majority of patients with Hodgkin's disease (HD) relapsing or progressing after combination chemotherapy. Prognostic factors reflecting unfavourable prognostic features of the disease as well as resistance to conventional salvage therapy have been identified. Preliminary data suggests a high efficacy of high-dose sequential chemotherapies in these patients. An ongoing randomized trial is comparing standard HDCT versus sequential HDCT in patients with relapsed HD. |
Josting, A.Nogova, L.Franklin, J.Glossmann, J. P.Eich, H. T.Sieber, M.Schober, T.Boettcher, H. D.Schulz, U.Muller, R. P.Diehl, V.Engert, A.
Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group
| Veröffentlicht: |
2005, J Clin Oncol, 23, 1522-9 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15632410 |
| Abstract: |
PURPOSE: To evaluate treatment outcome and prognostic factors in patients with refractory or first relapsed Hodgkin's disease (HD) treated with salvage radiotherapy (SRT) alone. PATIENTS AND METHODS: From 4,754 patients registered in the database of the German Hodgkin Study Group from 1988 to 1999, 624 patients were identified with progressive disease (n = 202), or with early (n = 170) or late (n = 252) relapsed HD. At first treatment failure, SRT alone was given to 100 patients. Patient characteristics were: median age, 36 years; progressive disease, 47%; early relapse, 23%; late relapse, 30%; and "B" symptoms, 14%. Eighty-five percent of the patients relapsed after cyclophosphamide, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP/ABVD) -like regimens; 8% after bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimens, 7% after first-line radiotherapy alone. RESULTS: The volume irradiated was mantle field in 43% of patients, inverted-Y in 8%, total nodal irradiation in 12%, and involved-field in 37%. The median SRT dose was 40 Gy (range, 15 to 50 Gy). Seventy-seven patients achieved a complete remission and four patients achieved a partial remission. The 5-year freedom from treatment failure and overall survival (OS) rates were 28% and 51%, respectively. In multivariate analysis, significant prognostic factors for OS were B symptoms (P = .018) and stage at relapse (P = .014). For freedom from second failure (FF2F) Karnofsky performance status (P = .0001) was significant. In patients with limited stage at progression/relapse, duration of first remission was significant (P = .04) for FF2F. CONCLUSION: SRT offers an effective treatment for selected subsets of patients with relapsed or refractory HD. |
Josting, A.Rudolph, C.Mapara, M.Glossmann, J. P.Sienawski, M.Sieber, M.Kirchner, H. H.Dorken, B.Hossfeld, D. K.Kisro, J.Metzner, B.Berdel, W. E.Diehl, V.Engert, A.
Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG)
| Veröffentlicht: |
2005, Ann Oncol, 16, 116-23 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15598948 |
| Abstract: |
BACKGROUND: We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD). PATIENTS AND METHODS: Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT). RESULTS: A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P <0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P=0.0127) were prognostic factors for FF2F. Response after DHAP (P <0.0081), duration of first remission (P=0.0017) and anemia (P=0.019) were significant for OS. CONCLUSION: Based on the promising results of this study, a prospective randomized European intergroup study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol). |
Josting, A.Sieniawski, M.Glossmann, J. P.Staak, O.Nogova, L.Peters, N.Mapara, M.Dorken, B.Ko, Y.Metzner, B.Kisro, J.Diehl, V.Engert, A.
High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study
| Veröffentlicht: |
2005, Ann Oncol, 16, 1359-65 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15939712 |
| Abstract: |
BACKGROUND: Combination chemotherapy can cure patients with non-Hodgkin's lymphoma (NHL), but those who suffer treatment failure or relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) can improve the outcome of these patients. We evaluated an intensified high-dose sequential chemotherapy program with a final myeloablative course. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, histologically proven primary progressive or relapsed aggressive NHL and eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40 mg (day 1-4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day 51); patients with partial (PR) or complete remission (CR) received cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and etoposide 500 mg/m2 (day 58-62). The final myeloblative course was BEAM: cytarabine 200 mg/m2 12q (day 81-84), etoposide 150 mg/m2 12q (day 81-84), melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT. RESULTS: Fifty-seven patients (median age 43 years, range 24-65) were enrolled: 23 (40%) patients were refractory to primary therapy and 34 (60%) patients had relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63% PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11% PR). Toxicity was tolerable. Median follow-up was 25 months (range 1-76 months). Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25% and 47% for all patients, respectively. FF2F at 2 years for patients with relapse and for patients refractory to primary therapy were 35% and 9% (P=0.0006), respectively. OS at 2 years for patients with relapse and for patients refractory to primary therapy were 58% and 24% (P=0.0044), respectively. CONCLUSIONS: We conclude that this regimen is feasible, tolerable and effective in patients with relapsed NHL. In contrast, the results in patients with progressive disease are unsatisfactory. This program is currently being modified by addition of rituximab for patients with relapsed aggressive NHL. |
Klimm, B.Diehl, V.Engert, A.
[In Process Citation]
Klimm, B.Diehl, V.Pfistner, B.Engert, A.
Current treatment strategies of the German Hodgkin Study Group (GHSG)
| Veröffentlicht: |
2005, Eur J Haematol Suppl, , 125-34 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16007881 |
| Abstract: |
Hodgkin's Lymphoma (HL) has developed to one of the best curable human cancers and overall about 80% of patients experience long-term disease free survival. Therefore, current treatment strategies aim at further improving treatment outcome, thereby trying to by minimize therapy-induced complications, such as infertility, cardiopulmonary toxicity, and secondary malignancies. Ongoing trials investigate a reduction of chemotherapy in terms of dose or cycles given, and the application of lower radiation doses and smaller radiation fields. For patients with a specific high-risk profile, new approaches with more intense drug combinations are currently being investigated. Moreover, the advent of effective salvage high-dose therapy for relapsed disease and a better understanding of prognostic factors have further improved the management of HL. Here, we summarize current strategies of the German Hodgkin Study Group (GHSG) in diagnostics and treatment of primary and relapsed HL, together with recent approaches for specific subgroups of HL patients. |
Klimm, B.Engert, A.Brillant, C.Eich, H. T.Mueller-Hermelink, H. K.Hermann, R.Ho, A.Hiddemann, W.Greil, R.Diehl, V.
Comparison of BEACOPP and ABVD chemotherapy in intermediate stage Hodgkin’s lymphoma: Results of the fourth interim analysis of the HD 11 trial of the GHSG
| Veröffentlicht: |
2005, J Clin Oncol, 23, 6507a |
| PubMedLink: |
|
| Abstract: |
Background: Combined modality treatment is the standard treatment for intermediate stage Hodgkin’s lymphoma (HL). Despite high complete remission (CR) rates, failure rates are remarkably higher in this group of patients. In the HD 11 multicenter trial of the GHSG the BEACOPP regimen was introduced to intermediate stages in an attempt to improve therapy outcome. Simultaneously, the possibility to reduce the IF-RT dose from 30 Gy to 20 Gy is evaluated. Methods: Between May 1998 and July 2002, 1363 patients (16–75 years old) with intermediate stage HL (CS I, IIA with risk factors or IIB with elevated ESR and/or >= 3 nodal areas) were randomised according to a 2 x 2 factorial design between: 4 ABVD + 30 Gy IF-RT (arm A), 4 ABVD + 20 Gy IF-RT (arm B), 4 BEACOPP basis + 30 Gy IF-RT (arm C), and 4 BEACOPP basis + 20 Gy IF-RT (arm D). Results: In the fourth interim analysis in August 2003, 1047 (77%) patients were evaluable for chemotherapy and 982 (72%) for radiotherapy. Patient characteristics were well balanced between the treatment arms with regard to age, gender, clinical stage, histopathology and performance status. 95.1% patients reached CR, 2.0% suffered from progression, the relapse rate was 5.9%, the mortality rate 3.2%. The most frequent haematological toxicity was leucopenia observed in 33% of patients (ABVD: 27%, BEACOPP: 40%). Infection rate was 5% (ABVD: 4%, BEACOPP:7%). Nine secondary neoplasias were observed: 2 AML, 3NHL, 4 solid tumors. After a median observation time of two years overall survival (OS) was 97.4% (95%-CI: 96–98) and freedom from treatment failure (FFTF) was 89.9% (95%-CI: 88–92). Both for FFTF and OS, there was no sequential significant difference either between ABVD and BEACOPP arms nor between 30 Gy and 20 Gy IF-RT arms. Conclusions: Thus far, no differences in treatment outcome were detected, neither between the two chemotherapy regimes nor between the different doses of radiotherapy. The low FFTF (89,9% at two years) led us to further intensification of chemotherapy by the introduction of 2 cycles of escalated BEACOPP (+ 2 ABVD) versus 4 ABVD in the subsequent HD14 trial for intermediate stage HL. |
Klimm, B.Engert, A.Diehl, V.
First-line treatment of Hodgkin's lymphoma
| Veröffentlicht: |
2005, , 4, 15-22 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15610655 |
| Abstract: |
Substantial clinical progress over the last decades has made Hodgkin's lymphoma (HL) into one of the most curable human cancers in adults. About 80% of patients in all stages and of all histological subtypes experience long-term disease-free survival. Modern treatment strategies aim to improve chemotherapy and radiotherapy, while minimizing therapy-related toxicities. Ongoing trials investigate a reduction of chemotherapy doses or cycles and the application of lower-radiation doses and smaller radiation field sizes. For patients with a specific high-risk profile, novel approaches with more intense drug combinations are currently being investigated in clinical trials. Here, we review recent approaches in the first-line treatment of early-favorable, early-unfavorable, and advanced-stage HL. |
Klimm, B.Reineke, T.Haverkamp, H.Behringer, K.Eich, H. T.Josting, A.Pfistner, B.Diehl, V.Engert, A.
Role of hematotoxicity and sex in patients with Hodgkin's lymphoma: an analysis from the German Hodgkin Study Group
| Veröffentlicht: |
2005, J Clin Oncol, 23, 8003-11 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16204002 |
| Abstract: |
PURPOSE: Several scores have described sex as a prognostic factor in patients with Hodgkin's lymphoma (HL). However, little is known how sex-specific factors influence treatment outcome. We systematically investigated sex differences with regard to pretreatment characteristics and therapy-related variables, and examined their influence on the outcome of HL patients. PATIENTS AND METHODS: This analysis comprises 4,626 HL patients of all prognostic risk groups who were enrolled onto the multicenter studies HD4 to HD9 of the German Hodgkin Study Group. At 5.5 years, 2,050 female and 2,576 male patients were analyzed. RESULTS: Male and female patients had similar prognostic factors. There was more acute chemotherapy-related hematotoxicity in women, especially more severe leucopenia (WHO grade 3/4, 69.9% female and 55.2% male; P < .0001). Importantly, this did not translate into more infections. Female patients had similar response rates but fewer relapses and deaths, leading to a significantly better freedom from treatment failure (FFTF; at 66 months, 81% female [95% CI, 79% to 82%] and 74% male [95% CI, 72% to 76%]). Severe leucopenia during chemotherapy was strongly associated with better FFTF, both for males and females. In addition, when only those patients who developed severe leucopenia within the first two cycles of chemotherapy were included, the factor maintained its protective role. CONCLUSION: The protective role of severe leucopenia suggests the testing of a more individualized therapy. In future trials, this therapy may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles. |
Klimm, B.Schnell, R.Diehl, V.Engert, A.
Current treatment and immunotherapy of Hodgkin's lymphoma
| Veröffentlicht: |
2005, Haematologica, 90, 1680-92 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16330443 |
| Abstract: |
The treatment of Hodgkin's lymphoma has changed significantly over the last decades, rendering this entity one of the most curable human cancers. To date, about 80% of patients achieve long-term disease-free survival. Current strategies in first-line treatment aim at further improving outcome and thereby preventing therapy-induced complications, such as infertility, cardiopulmonary toxicity, and secondary malignancies. Ongoing trials for patients in early stages are investigating lower radiation doses and smaller radiation fields and possible reductions in the doses or number of cycles of chemotherapy given. For patients in advanced stages, new drug combinations with higher dose density and intensity have been developed, and are currently being evaluated in clinical trials. Approaches for relapsed Hodgkin's lymphoma comprise salvage radiotherapy, salvage chemotherapy and high-dose chemotherapy followed by autologous stem cell transplantation. In recent years, the introduction of effective salvage high-dose therapy and a better understanding of prognostic factors have remarkably improved the management of relapsed Hodgkin's lymphoma. For multiple pretreated patients antibody-based agents that showed promising results in experimental models are being investigated in clinical trials. Radioimmunoconjugates and monoclonal antibodies have demonstrated some clinical efficacy. Here, we review new aspects in the treatment of primary and relapsed Hodgkin's lymphoma as well as recent immunotherapeutic approaches. |
Meyer, R. M.Gospodarowicz, M. K.Connors, J. M.Pearcey, R. G.Bezjak, A.Wells, W. A.Burns, B. F.Winter, J. N.Horning, S. J.Dar, A. R.Djurfeldt, M. S.Ding, K.Shepherd, L. E.
Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group
| Veröffentlicht: |
2005, J Clin Oncol, 23, 4634-42 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15837968 |
| Abstract: |
PURPOSE: We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma. PATIENTS AND METHODS: Patients with nonbulky clinical stage I to IIA Hodgkin's lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles. RESULTS: We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P = .006; 93% v 87%); no differences in event-free survival (P = .06; 88% v 86%) or overall survival (P = .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P = .004; 95% v 88%); no difference in overall survival was detected (P = .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin's lymphoma or acute treatment-related toxicity. CONCLUSION: In patients with limited-stage Hodgkin's lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin's lymphoma or acute treatment-related toxicity. |
Mikhaeel, N. G.Hutchings, M.Fields, P. A.O'Doherty, M. J.Timothy, A. R.
FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma
| Veröffentlicht: |
2005, Ann Oncol, 16, 1514-23 |
| PubMedLink: |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15980161 |
| Abstract: |
BACKGROUND: Less than 50% of all high-grade non-Hodgkin lymphoma (NHL) patients experience lasting disease-free survival. Risk-adapted treatment strategies require better tools for prediction of outcome. This investigation aimed to assess the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two to three cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: One hundred and twenty-one patients with high-grade NHL underwent FDG-PET. The therapy response on FDG-PET was correlated to PFS and OS using Kaplan-Meier survival analysis. Cox regression analyses were employed to test for independence of known pretreatment prognostic factors. RESULTS: Fifty FDG-PET scans were negative, 19 scans showed minimal residual uptake (MRU), and 52 scans were positive. The estimated 5 year PFS was 88.8% for the PET-negative group, 59.3% for the MRU group, and 16.2% for the PET-positive group. Kaplan-Meier analyses showed strong associations between FDG-PET results and PFS (P <0.0001) and OS (P <0.01). Early interim FDG-PET was independent of the other prognostic factors. CONCLUSIONS: Early interim FDG-PET is an accurate and independent predictor of PFS and OS. An early assessment of chemotherapy response with FDG-PET could provide the basis for selection of patients for alternative therapeutic strategies. |
Nogova, L.Reineke, T.Eich, H. T.Josting, A.Muller-Hermelink, H. K.Wingbermuhle, K.Brillant, C.Gossmann, A.Oertel, J.Bollen, M. V.Muller, R. P.Diehl, V.Engert, A.
Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG)
|
