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

A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin-Frankfurt Munster (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 therapyrelated 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 470 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.