GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AFTER INITIAL CHEMOTHERAPY FOR ELDERLY PATIENTS WITH PRIMARY ACUTE MYELOGENOUS LEUKEMIA

Background. Elderly patients with primary acute myelogenous leukemia ( AML) are less likely to enter remission than younger adults, in part b ecause of a higher mortality rate related to severe myelosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been sho wn to shorten the duration of neutropenia and decrease infectious comp lications when administered after chemotherapy to patients with lympho mas and solid tumors. Methods. We randomly assigned 388 patients 60 ye ars of age or older who had newly diagnosed primary AML to receive pla cebo or GM-CSF (5 mu g per kilogram of body weight per day intravenous ly) in a double-blind manner, beginning the day after the completion o f three days of daunorubicin and seven days of cytarabine. If leukemic cells persisted in the marrow three weeks after the initiation of che motherapy, further daunorubicin (two days) and cytarabine (five days) were administered. GM-CSF or placebo was given daily until the neutrop hil count was at least 1000 per cubic millimeter, there was evidence o f the regrowth of leukemia, or severe toxic effects attributable to th e study infusion occurred. Patients who had a complete remission were then randomly assigned to receive one of two intensification regimens. Results. Of 388 patients (median age, 69 years), 193 were randomly as signed to receive GM-CSF and 195 to receive placebo. The rate of compl ete remission was 51 percent (95 percent confidence interval, 44 to 59 percent) among those assigned to GM-CSF and 54 percent (95 percent co nfidence interval, 47 to 61 percent) among those assigned to placebo ( P = 0.61). The reasons for failure (early death, death during marrow h ypoplasia, and persistent leukemia), the incidence of severe or lethal infection, and the incidence of the regrowth of leukemia (2 percent o verall) were similar in the two groups. The median duration of neutrop enia was slightly shorter (P = 0.02) in the patients who received GM-C SF (15 days) than in those who received placebo (17 days), but the cli nical importance of this result was minimal because the growth factor failed to lower the treatment-related mortality rate or improve the ra te of complete remission. Conclusions. GM-CSF, in the dose and schedul e we used, does not stimulate the regrowth of leukemia, but it also do es not decrease the severe myelosuppressive consequences of initial ch emotherapy or improve the response rate in patients 60 years of age or older with primary AML. It should not be recommended for use in such patients.