Granulocyte-Macrophage Colony-Stimulating Factor During and After Remission Induction Treatment for Elderly Patients with Acute Myeloid Leukemia

From May 1992 to November 1994, 240 patients with de novo acute myeloid leukemia (AML) and aged 55–75 years (median 68 years) were enrolled in a multicenter, double-blind randomized study comparing placebo and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Escherichia coli derived) (5/µg/kg per day 6-h infusion) during induction chemotherapy (idarubicin 8 mg/m2 per day i.v. on days 1–5 plus cytarabine, ara-C, 100 mg/m2 per day continuous infusion on days 1–7) and until recovery of a neutrophil count > 0.5 x 109/1. Post-remission therapy was identical in the two arms. The two groups were comparable regarding the following parameters: age, sex, performance status, fever, organomegaly, initial blood cell counts, French-American-British (FAB) classification, presence of myelodysplastic features, and incidence of karyotypic abnormalities. Of the 209 patients currently evaluable, 130 (62%) achieved complete remission (CR) with no significant difference between patients aged 55–64 (57/90 = 63%) and patients aged 65 to 75 years (73/119 = 61%). There were 17 (8%) early deaths, 18 (9%) deaths in aplasia, and 45 (21%) failures. No significant difference was observed between the GM-CSF group (n = 103) and the placebo group (n = 106) regarding the CR rate (63% vs. 61%), the incidence of early deaths (10% vs. 6%), of deaths in aplasia (8% vs. 9%), and of failures (19% vs. 24%). The duration of neutropenia was shorter in the GM-CSF group (median 22 days vs. 26 days, p = 0.002). However, the incidence of febrile episodes and of bacteriemias and the duration of hospitalization was similar in the two groups. With a median follow up of 19 months, the overall survival of all eligible patients was similar in both groups (39% actuarial survival at 2 years in the GM-CSF group vs. 33% in the placebo group, p = 0.45 log-rank test). Nonetheless, the disease-free survival was longer for patients who achieved CR in the GM-CSF group (44% continuous CR rate at 2 years vs. 19%, p = 0.024). The study medication was prematurely stopped due to toxicity in 17 patients (14 GM-CSF, three placebo; p = 0.003). We conclude that (a) the induction treatment with idarubicin and conventional doses of ara-C obtains a high CR rate in elderly patients (b) the administration of GM-CSF during and after induction chemotherapy results in a faster recovery of neutrophils but does not reduce infectious toxicity and increases neither the efficacy of this chemotherapy nor the overall survival. However, the disease-free survival was significantly longer for patients who received GM-CSF before achieving CR.