Adult life after surviving lymphoma in childhood

Almost all pediatric lymphomas are malignant, high-grade tumors. The combined incidence of Hodgkin’s disease (HD) and non-Hodgkin lymphoma (NHL) reaches 10 to 12 new cases a year per million children under the age of 16 years, representing about 10% of all pediatric cancers. HD makes up to 40% and NHL 60% of pediatric lymphomas. During the last 20 years, cure rates raised dramatically so that currently over 90% of children and adolescents with HD and about 80% of those with NHL can be cured. As cure can be achieved in a large majority of patients, long-term effects and quality of life of the survivors are nowadays the principal challenges to pediatric oncologists.

Like survivors from acute lymphoblastic leukemia, young adults cured from NHL may present with neurocognitive deficits, especially if treated at a young age and with cranial irradiation. Intrathecal or high-dose intravenous chemotherapy with methotrexate may induce the same problems, although in a lesser extent and severity. Large enough prospective cohort studies like the CCSS in the USA were able to show an increased risk of second malignant neoplasms, especially brain tumors in patients formerly treated with cranial irradiation. Reduced fertility can follow exposure to cyclophosphamide, especially in the male. Cardiac function must be serially evaluated over the long to very long-term because of potential cardiomyopathy after high anthracycline doses and/or mediastinal irradiation.

Survivors from HD are at high risk of late complications. Radiation therapy to the neck and mediastinum (mantle field) induces a 50% risk of developing hypothyroidism and a 20% risk of developing thyroid nodules at 20 years. The risk of thyroid cancer is 18 times higher the expected rate for the general population. Secondary aggressive breast cancer shows a cumulative risk of 30% at 30 years after radiotherapy. Other structures affected by mediastinal irradiation are the heart (pericardial, myocardial and endocardial structures), the great arteries (fibrosis, stenosis, aneurysms) and the central portion of the lungs (diffusion troubles, restrictive pneumopathy). Cardiac toxicity can be enhanced by the concomitant therapy with adriamycin and lung toxicity by bleomycin. Radiotherapy to the paraaortic and iliacal lymph nodes can affect gonadal function both in males and females; concomitant chemotherapy with alkylating agents like cyclophosphamide and especially procarbazine have a synergistic action and can lead to premature menopause as well as infertility.

Although the vast majority of survivors from pediatric lymphomas fare well, a minority present with extreme symptoms of depression and psychosomatic distress; female sex, low socio-economic status and treatment with intensive chemotherapy are important risk factors for a poor psychosocial outcome.

It is therefore crucial, but not always easy, to inform patients and families about potential late effects and organize follow-up after the pediatric age. A well functioning network of pediatric oncologists, GP’s, adult oncologists and other specialists of adult medicine must be developed in order to prevent, early detect and treat expected long-term toxicities.