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

Abstract

A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin-Frankfurt-Mü nster (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 5072, 6173 and 5772%, 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.

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

“…Table 2 shows that patients with MLL-rearranged AML have an intermediate outcome, with a 5y-pEFS (probability of EFS at 5 years from diagnosis) ranging from 32 to 54% and a 5y-pOS (probability of OS at 5 years from diagnosis) ranging from 42 to 62%. 4,5,[69][70][71][72][73][74][75][76][77] Currently, hematopoietic stem cell transplantation is no longer advised in first remission. Recently, we identified the t(1;11)(q21;q23) subgroup as a new prognostic subgroup in pediatric AML.…”

Acute Myeloid Leukemia in Children: Experience from Tertiary Cancer Centre in India

“…Complete remission (CR) rates as high as 90 % and overall survival (OS) rates up to 65 % have been reported in pediatric AML [1,2]. There is no standard induction chemotherapy regime for treatment of pediatric AML.…”

Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML

“…Details of these treatment protocols and overall outcome data have been published earlier, with the exception of study AML-BFM 04, which is ongoing. [22][23][24] In these protocols, treatment consisted of four to five blocks of intensive chemotherapy, using a standard cytarabine and anthracycline backbone. Stem cell transplantation (SCT) in first complete remission (CR1) was used only in selected high-risk patients.…”