Abstract
In a multicenter trial, 259 young adults (15-49 years) with newly diagnosed acute myeloid leukemia (AML) were first randomized to receive a timed-sequential induction regimen given either alone (135 patients) or concomitantly with granulocyte-macrophage colony-stimulating factor (GM-CSF) (124 patients). Patients reaching complete remission (CR) were then randomized to compare a timed-sequential consolidation to a postremission chemotherapy including four cycles of high-dose cytarabine followed by maintenance courses. In the appropriate arm, GM-CSF was given concurrently with chemotherapy during all cycles of consolidation. CR rates were significantly better in the GM-CSF arm (88 vs 78%, P<0.04), but did not differ after salvage. Patients receiving GM-CSF had a higher 3-year event-free survival (EFS) estimate (42 vs 34%), but GM-CSF did not impact on overall survival. Patients with intermediate-risk cytogenetics benefited more from GM-CSF therapy (P=0.05) in terms of EFS than patients with other cytogenetics. This was also confirmed when considering only patients following the second randomization, or subgroups defined by a prognostic index based on cytogenetics and the number of courses required for achieving CR. Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML.
Publication types
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Comparative Study
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Adolescent
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Adult
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Amsacrine / administration & dosage
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Amsacrine / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Cell Division / drug effects
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Combined Modality Therapy
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Cytarabine / administration & dosage
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Cytarabine / adverse effects
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Daunorubicin / administration & dosage
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Daunorubicin / adverse effects
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Disease-Free Survival
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Drug Administration Schedule
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Female
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Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
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Hematopoietic Stem Cell Transplantation
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Humans
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Kaplan-Meier Estimate
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Leukemia, Myeloid / drug therapy*
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Leukemia, Myeloid / genetics
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Leukemia, Myeloid / pathology
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Leukemia, Myeloid / surgery
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Male
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Middle Aged
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Mitoxantrone / administration & dosage
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Mitoxantrone / adverse effects
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Neoplastic Stem Cells / drug effects
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Premedication*
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Proportional Hazards Models
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / pharmacology
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Risk
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Salvage Therapy
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Stimulation, Chemical
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Transplantation, Homologous
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Treatment Outcome
Substances
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Recombinant Proteins
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Amsacrine
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Cytarabine
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Granulocyte-Macrophage Colony-Stimulating Factor
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molgramostim
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Mitoxantrone
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Daunorubicin