Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: results of AML-BFM 98.

Abstract

PURPOSE:

To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone).

PATIENTS AND METHODS:

Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy.

RESULTS:

Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%).

CONCLUSION:

Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.

• Authors: Ursula Creutzig, Martin Zimmermann, Thomas Lehrnbecher, Norbert Graf, Johann Hermann, Charlotte M Niemeyer, Alfred Reiter, Jörg Ritter, Michael Dworzak, Jan Stary, Dirk Reinhardt
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 27 Pg. 4499-506 (Sep 20 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16983120 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cytarabine
• Granulocyte Colony-Stimulating Factor
• Mitoxantrone
• Idarubicin
• Daunorubicin

Topics

• Acute Disease
• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Cranial Irradiation
• Cytarabine (administration & dosage, adverse effects)
• Daunorubicin (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage, therapeutic use)
• Humans
• Idarubicin (administration & dosage, adverse effects)
• Infant
• Infections (etiology)
• Leukemia, Myeloid (drug therapy, mortality, pathology)
• Male
• Mitoxantrone (administration & dosage, adverse effects)
• Neutropenia (chemically induced, prevention & control)
• Radiotherapy, Adjuvant
• Risk Assessment
• Risk Factors
• Survival Analysis
• Treatment Outcome