Adverse reactions and late effects

Both chemotherapy and radiotherapy may cause adverse reactions (side-effects). Acute adverse reactions occur during or immediately after treatment. In contrast to that, late effects may occur even a long time after the end of treatment. While acute adverse reactions usually disappear after a while or can be prevented or at least mitigated to a large extent during treatment, late effects may often have a drastic impact on the patient’s quality of life and are therefore of great importance.

Chemotherapy

The intensity of acute adverse reactions to chemotherapy can be quite different from patient to patient. Nausea and vomiting appearing several hours after the administration of chemotherapeutic drugs can be considerably alleviated by antiemetic drugs. Loss of hair is an adverse reaction that affects most patients. However, it is usually a temporary problem, and permanent loss of hair is seen very rarely.

Blood

Chemotherapeutic drugs impair the function of the bone marrow, which has important influence on the conduction of therapy. This impairment causes changes in the blood count (hemogram), which should be controlled in detail very regularly. A decrease of the white blood cell count (leukocytes) is associated with an increased risk to contract infectious diseases, especially oral or nasal infections or pneumonia. New drugs, which are injected subcutaneously, may reduce the time of increased infection risk. In very rare cases, spontaneous bleedings caused by a low platelet count have been observed. A decrease in the red blood cell count (erythrocytes) can lead to symptoms like general weakness, fatigue and dyspnea (shortness of breath). Nevertheless, blood transfusions are usually not necessary. Before the start of a new chemotherapy cycle, the blood count values should have recovered.

Fertility and hormonal balance

It seems to depend on the dosage of some of the used drugs if male patients become permanently infertile as consequence of chemotherapy or not. The physician must inform his patient about these consequences, especially young male patients who want to have children, and should discuss the possibility to cryo-conserve (freeze) sperm before the start of treatment.

Female patients have to be informed about a premature onset of the menopause. It depends on the patient’s age and the dosage of the administered cytostatic drugs if the ovaries recover and if the woman becomes capable of conception again. Even one year after the end of treatment, a return of menstruation is possible. However, to reduce the danger of a premature onset of osteoporosis (reduction in bone density), a lack of estrogens (female hormones) should be temporarily or permanently balanced if corresponding complaints occur. When treatment is complete, it is advised to consult a physician who is specialized in dealing with the mentioned symptoms and problems (gynecologist, endocrinologist).

Before the start of treatment, a detailed menstruation history and a hormonal analysis should be conducted. In this context, the so-called anti-Müllerian hormone is subject to recent research activities. This hormone seems to be a marker for the ovarian reserve (the number of oocytes with the ability to mature).

Oral contraceptives (the Pill) or so-called GnRH analogues may protect the ovaries, and their administration should be considered. Both influence the ovarian cycle and inhibit the maturation of oocytes, through which a damage of the ovarian function and the oocytes may possibly be prevented. In addition, it is possible to remove mature oocytes and to cryo-conserve them (either fertilized or unfertilized). The cryo-conservation of ovarian tissue may also be an option.

There is no evidence that female patients who become pregnant after the end of therapy have an increased risk for abnormal embryonic developments.

Heart and lung function

Certain drugs contained in chemotherapy regimens can affect the heart and lung function. An impairment of the heart function is mostly dose-dependent and also influenced by other individual factors. Pump function, cardiac rhythm and blood circulation in the coronary vessels can be affected. Acute symptoms are reversible in almost all cases. However, cardiac symptoms occurring after the end of treatment are often persistent. The lung function can also be adversely affected by inflammations or changes of the lung tissue. A severe impairment of the lung function is mostly also dose-dependent. Inflammations of the pulmonary alveoli appear quite rarely and are not dose-dependent. Because of the potential adverse reactions mentioned above, thorough examinations regarding heart and lung function should be conducted at the beginning of therapy and within the scope of follow-up care.

Nervous system

During chemotherapy, dysesthesia of hands and feet (distortions of the sense of touch) can occur, often in the form of creeping or furry sensations. Depending on the degree of these symptoms, the drug that causes them can be replaced or discontinued.

Radiotherapy

Also radiotherapy can provoke acute adverse reactions, depending on the radiation fields and the applied radiation doses. The involved-field radiotherapy that is used today rarely causes strong adverse reactions. During radiotherapy, red skin or inflammations of the mucous membranes may occur, but these symptoms usually disappear after the end of therapy.

Heart and lung

After a radiation of the thorax (mediastinal radiation), a temporary radiation damage of the lung (pulmonary fibrosis) is a frequently detected consequence, but in most cases it does not cause clinical complaints. In rare cases, radiation-induced, non-infectious inflammations (radiation pneumonitis, myocarditis, percarditis) have been observed. They can occur weeks or months after radiation of the mediastinum and cause substantial complaints and a long-term impairment of the general condition. Problems with the coronary vessels similar to a coronary heart disease may occur month or even years after radiotherapy, but can be treated by means of certain drugs. However, there aren’t any recently published research data on these severe side-effects yet. We only have references in this context concerning extended field radiation (with radiation doses of 40 45 Gy), which is no longer applied today.

Thyroid gland

Some patients who underwent radiation of the cervical (neck) lymph nodes are diagnosed with dysfunctions of the thyroid gland. These dysfunctions become manifest in a hypofunction with relatively unspecific symptoms like general weakness, fatigue, freezing, weight gain or a lack of concentration. A hypofunction of the thyroid gland must be treated by substituting thyroid hormone.

Fertility

In women between 35 and 45 years of age, a premature onset of the menopause has to be expected after radiation of the pelvis. Frequently observed symptoms are hot flashes, sweating, tachycardia (heart hurry) and sleep disorders. In younger patients, menopausal symptoms are reported only rarely, and if they occur, they often disappear again after some time. Theoretically, male patients can become temporarily infertile as well. The procreative capacity may recover up to three years after the end of therapy.

It is important to note that there is no evidence for an increased risk of abnormalities in children whose parents were successfully treated with chemo- and radiotherapy, i.e. abnormal embryonic developments do not occur more often than in children of healthy parents. So there is no reason to discourage women who have been cured from Hodgkin lymphoma from becoming pregnant.

Secondary tumors (secondary malignancies/ neoplasias)

The most severe late effect of both chemotherapy and radiotherapy is the increased risk to come down with secondary tumors (Non-Hodgkin lymphomas, leukemias, solid tumors). That is the reason why lifelong aftercare and cancer screening examinations in Hodgkin lymphoma patients are of great importance.

By optimizing the treatment methods in Hodgkin lymphoma, currently ongoing clinical trials aim to reduce the frequency of adverse reactions and late effects as well as the risk of secondary tumors without losses in efficacy.