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Clinical Trial
. 2005 Dec;19(12):2030-42.
doi: 10.1038/sj.leu.2403920.

Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials

U Creutzig  1 , M Zimmermann, J Ritter, D Reinhardt, J Hermann, G Henze, H Jürgens, H Kabisch, A Reiter, H Riehm, H Gadner, G Schellong
Affiliations
Clinical Trial

Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials

U Creutzig et al. Leukemia. 2005 Dec.

Abstract

A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin-Frankfurt-Münster (BFM) studies from 1978 to 1998. The first cooperative trial AML-BFM 78 established intensive chemotherapy with seven drugs, CNS irradiation and 2-year maintenance, achieving a long-term survival (overall survival (OS)) of 40%. Induction intensification in AML-BFM 83 resulted in significant improvement of disease-free survival (DFS). The risk of haemorrhage, especially in children with hyperleukocytosis, proved the high relevance of supportive care. In AML-BFM 87, the benefit of CNS irradiation in preventing CNS/systemic relapses was demonstrated. In AML-BFM 93, the introduction of idarubicin during first induction followed by intensification with HAM increased the 5-year EFS, DFS and OS to 50+/-2, 61+/-3 and 57+/-2%, respectively. Stem cell transplantation (SCT), as applied in high-risk patients with a matched related donor, did not significantly improve the outcome compared to chemotherapy alone. In spite of treatment intensification, the therapy-related death rate decreased from trial to trial, mainly during induction. The future aim is to reduce long-term sequelae, especially cardiotoxicity, by administration of less cardiotoxic drugs, and toxicity of SCT by risk-adapted indications. The AML-BFM studies performed in three European countries with >70 cooperating centres have significantly improved the outcome in AML children; nevertheless, increasing experience with these intensive treatment regimens is of fundamental importance to reduce fatal complications.

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