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-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.
Creutzig
U
U
Department of Haematology, Oncology, University Children's Hospital, Münster, Germany. ursula.creutzig.de
Zimmermann
M
M
Ritter
J
J
Reinhardt
D
D
Hermann
J
J
Henze
G
G
Jürgens
H
H
Kabisch
H
H
Reiter
A
A
Riehm
H
H
Gadner
H
H
Schellong
G
G
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D024221:Antineoplastic Protocols / Q000592:standards*; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D012074:Remission Induction / Q000379:methods; D018570:Risk Assessment; D055502:Secondary Prevention; D016896:Treatment Outcome