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Klin Padiatr 2013; 225(S 01): S79-S86
DOI: 10.1055/s-0033-1337968
Zum 80. Geburtstag von Prof. Riehm
© Georg Thieme Verlag KG Stuttgart · New York

Development of a Curative Treatment within the AML-BFM Studies[*]

Entwicklung einer kurativen Therapie im Rahmen der AML-BFM-Studien
U. Creutzig
1   Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
,
M. Zimmermann
1   Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
,
M. N. Dworzak
2   Department of Paediatrics Medical University of Vienna, St. Anna Children’s Hospital and Children’s Cancer Research ­Institute, Vienna, Austria
,
J. Ritter
3   Deparment of Paediatric Haematology and Oncology, University Children’s Hospital, Münster, Germany
,
G. Schellong
3   Deparment of Paediatric Haematology and Oncology, University Children’s Hospital, Münster, Germany
,
D. Reinhardt
1   Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
22. Mai 2013 (online)

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Abstract

The first multicenter treatment study for AML in childhood in Germany was performed from 1978 onwards. The therapy plan was designed similar to that for the acute lymphoblastic leukaemia (ALL). The drugs with the highest efficacy in AML, cytarabine cutting catara-bine and anthracyclines, were combined during induction and consolidation, followed by preventive cranial irradiation and maintenance therapy similar to that in ALL. The remission rate of the initial study was 80%, and the 5-year survival rate increased from less than 10% before 1970 to 40%. 5 subsequent trials have further increased the 5-year survival to now 70% and even 90% in the subgroup of core-binding factor leukaemias by using an intensified and optimised treatment schedule.

The AML-BFM studies were the only prospective study sequence testing the benefit of cranial irradiation. Results from study -87 including the non-randomized patients showed an increased risk of CNS and/or bone marrow relapses in non-irradiated patients. Later on there was evidence that 12 Gy resulted in the same relapse rate as 18 Gy. The AML-BFM studies always used the experience from the previous study to optimize the next study. This approach was essential together with improved supportive treatment and experience of the medical staff for the step-wise and considerable increase of longterm survival within the 6 subsequent AML-BFM studies.

Zusammenfassung

Die erste multizentrische Therapiestudie bei Kindern mit AML in Deutschland wurde 1978 unter der ­Leitung von G. Schellong begonnen. Die Therapiestrategie war anfangs ähnlich aufgebaut wie die der akuten lympho­blastischen Leukämie (ALL), wobei die bei der AML verstärkt wirksamen Substanzen Cytarabin und Anthrazykline in den Induktions- und Konsolidierungsphasen stärker gewichtet wurden. Eine präventive Schädelbestrahlung und eine Erhaltungstherapie wurden ebenfalls nach dem Muster der ­ALL-Therapie gegeben. Fast 80% der Patienten erreichten eine Remission, und die 5-Jahres-Überlebensrate konnte von unter 10% vor 1970 auf 40% angehoben werden. In den weiteren Studien wurde die Therapie deutlich in­tensiviert und optimiert, so dass heute eine 5-Jahresüberlebensrate von 70% möglich ist. Sie liegt sogar bei 90% in der Gruppe der „Core-Bin­ding“ Faktor Leukämien.

Die AML-BFM Studiengruppe ist die einzige, die die Wirksamkeit der Schädelbestrahlung geprüft hat. Ergebnisse der Studie -87 zeigten unter Einschluss der nicht-randomisierten Patienten ein erhöhtes Risiko für Rezidive im Zentralnervensystem (ZNS) und/oder Knochenmark bei nicht bestrahlten Patienten. Später konnte gezeigt werden, dass die Ergebnisse mit 12 Gy oder 18 Gy gleich sind. In den AML-BFM-Studien wurden jeweils die Erfahrungen der Vorgängerstudie zur Optimierung der folgenden Studie genutzt. Dieses Vorgehen hat ganz entscheidend, zusammen mit der Verbesserung der supportiven The­rapie und dem Erfahrungsgewinn der Teilnehmer, zu dem beträchtlichen Anstieg der Langzeitüberlebensraten im Rahmen der sechs aufeinanderfolgenden AML-BFM Therapiestudien geführt.

Key words

acute myeloid leukaemia - children - AML-BFM studies - diagnosis - treatment

Schlüsselwörter

akute myeloische Leukämie - Kinder - AML-BFM Studien - Diagnose - Behandlung
*

* supported by the Deutsche Krebshilfe e.V.


 

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