Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: A randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group

Purpose: To assess the value of granulocyte-macrophage colony-stimulating factor (GM-CSF) for induction treatment of acute myeloid leukemia (AML), both for priming of leukemic cells and for acceleration of hematopoietic recovery. Patients and Methods: GM-CSF was administered 5 mu g/kg/d by continuous intravenous (IV) infusion during induction therapy with daunorubicin (DNR) (days 1 to 3) and cytarabine (ARA-C) (days 1 to 7). A total of 102 patients were randomized onto four arms, as follows: (1) GM-CSF 24 hours before and during chemotherapy (arm +/-); (2) GM-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes (PMNs) (arm -/+); (3) GMCSF before, during, and after chemotherapy (arm +/+); or (4) no GM-CSF (arm -/-). Stopping rules were applied in case of an initial WBC count greater than 30 x 10(9)/L or ct secondary increase of circulating blast cells, Analyses were performed according to the intention-to-treat principle. Results: The complete remission (CR) rates were 77% (arm -/-), 72% (arm +/-), 48% (arm -/+), and 46% (arm +/+). patients randomized to receive GM-CSF after induction (arms -/+ and +/+) had a significantly lower CR rate (P = .008) and a trend toward accelerated recovery of neutrophils, but no fewer infections or induction deaths. The lower CR rate appeared to be related to an increased resistance rate, with persistent leukemia. The main side effects of GM-CSF were fluid retention and hypotension. Conclusion: GM-CSF administered during induction treatment of AML with a DNR/Ara-C combination did not provide any clinical benefit. Furthermore, there wets a significant decrease in the CR rate with more persistent leukemia when GM-CSF was administered during the hypoplastic phase after the chemotherapy courses.