Effect of priming with granulocyte-macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group.
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.
Thomas
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Department of Hematology, Hôpital Edouard Herriot, Lyon, France. xavier.thomas@chu-lyon.fr
Raffoux
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Arnaud
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de Revel
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Terré
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Gardin
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Quesnel
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Bourhis
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Elhamri
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Fenaux
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Preudhomme
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Michallet
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Castaigne
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Dombret
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D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011292:Premedication; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012306:Risk; D016879:Salvage Therapy; D013268:Stimulation, Chemical; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D011994:Recombinant Proteins; D000677:Amsacrine; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C082430:molgramostim; D008942:Mitoxantrone; D003630:Daunorubicin