Non-Hodgkin lymphoma in children and adolescents

Until the 1970s, childhood non-Hodgkin lymphoma (NHL) was an almost incurable disease. Since then tremendous progress has been made. In this article the contributions of the Berlin-Frankfurt-Münster (BFM)-group clinical studies to the development of efficacious treatment for childhood and adolescent NHL will be described.From 1975 to 2001, 6 consecutive cooperative multicenter studies were conducted into which a total of 2 190 protocol patients were enrolled. The probability of event-free survival (pEFS) at 5 years was 60% in the first study and increased to 84% in study NHL-BFM 95 while the overall survival probability increased from 65 to 89%. Landmarks in the development were the recognitions that childhood NHL is a heterogeneous disease and different biological subtypes require specifically adapted treatment strategies, that within subtypes the required treatment intensity varies significantly and that the appropriate prognostic parameters for stratification of treatment intensity differ between different NHL subentities. With increasing efficacy of chemotherapy local therapy modalities were almost completely abandoned. Central nervous system (CNS) irradiation for prevention of CNS relapses was, with few exceptions, replaced by CNS directed chemotherapy. The key role of methotrexate and its optimal risk adapted dose and administration schedule for treatment of mature B-cell neoplasm's could be enlightened and the first phase 2 study proving the activity of the anti-CD20 monoclonal antibody Rituximab as targeted therapy for pediatric B-NHL was successfully conducted.