Non-Hodgkin Lymphoma in Children and Adolescents

Abstract

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.

Zusammenfassung

Bis 1975 war die Überlebensprognose von Kindern mit Non-Hodgkin Lymphomen (NHL) fast infaust. Seitdem wurde ein enormer Fortschritt in der Behandlung erzielt. Die Beiträge der Berlin-Frankfurt-Münster (BFM) Therapiestu­dien zur Entwicklung einer wirksamen Therapie der NHL des Kindes- und Jugendalters sollen in diesem Beitrag beschrieben werden.

Von 1975 bis 2001 wurden 6 aufeinanderfolgende kooperative multizentrische Therapie­studien durchgeführt, in die 2 190 Protokoll Patienten aufgenommen wurden. Die Wahrscheinlichkeit des ereignisfreien Überlebens (pEFS) nach 5 Jahren war in der ersten Studie 60% und stieg auf 84% in der Studie NHL-BFM 95 und die Überlebenswahrscheinlichkeit stieg von 65 auf 89%. Die wichtigsten Entwicklungsschritte waren die Erkenntnis, dass die NHL des Kindes­alters sehr heterogen sind und jede biologische Subgruppe eine speziell angepasste Therapieform erfordert, dass innerhalb der Subtypen die erforderliche Therapieintensität interindividuell stark variiert und dass die zur Stratifizierung der Therapieintensität geeigneten prognostischen Parameter je nach Entität sehr unterschiedlich sind. Parallel zur Optimierung der Chemotherapie wurden lokale Therapiemaßnahmen fast vollständig eliminiert und die Bestrahlung des ZNS durch eine optimierte ZNS-wirksame Che­motherapie weitestgehend ersetzt. Als Beitrag zur Aufklärung des Stellenwertes der einzelnen eingesetzten Medikamente konnte die Schlüsselrolle von Methotrexat für den Therapieerfolg bei reifen B-Zell Neoplasien herausgearbeitet und seine risikoadaptiert optimale Dosis und Verabreichungsform definiert werden. In einer Phase 2 Studie konnte zudem erstmals die Wirksamkeit des anti-CD20 Antikörpers Rituximab bei kindlichen B-Zell Lymphomen im Sinne einer targeted therapy gezeigt werden.

Key words

non-hodgkin lymphoma (NHL) - prognostic factors - treatment response - immunotherapy

Schlüsselwörter

Non-Hodgkin Lymphome (NHL) - prognostische Faktoren - Therapieansprechen - Immuntherapie

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