USE OF RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR DURING AND AFTER REMISSION INDUCTION CHEMOTHERAPY IN PATIENTS AGED 61 YEARS AND OLDER WITH ACUTE MYELOID-LEUKEMIA (AML) - FINAL REPORT OF AML-11, A PHASE-III RANDOMIZED STUDY OF THE LEUKEMIA COOPERATIVE GROUP OFANIZATION-FOR-THE-RESEARCH-AND-TREATMENT-OF-CANCER (EORTC-LCG) AND THE DUTCH BELGIAN HEMATOONCOLOGY COOPERATIVE GROUP (HOVON)

We conducted a prospective randomized multicenter clinical trial compa ring the effects of granulocyte-macrophage colony-stimulating factor ( GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 year s and older with untreated newly diagnosed acute myeloid leukemia (AML ). Patients were randomized to either receive daunomycin-cytosine arab inoside with GM-CSF or daunomycin-cytosine arabinoside (control arm). Based on the rationale that GM-CSF might sensitize the leukemic cells to the cytotoxicity of chemotherapy as well as enhance white blood cel l regeneration, GM-CSF was given during chemotherapy as well as after chemotherapy. Patients were treated with one, and in case of a partial response, with two remission induction cycles. When a complete remiss ion was attained they received one additional cycle of consolidation t herapy. Of 318 evaluable patients with a median age of 68 years, 157 w ere randomized to receive GM-CSF and 161 were assigned to control ther apy. The effect of GM-CSF on treatment was evaluated according to inte ntion-to-treat. Complete remission was achieved in 56% of the patients in the GM-CSF group and 55% of the control patients (P = .98). Recove ry of neutrophils was significantly faster in GM-CSF-treated patients. The median time of recovery of neutrophils towards 0.5 x 10(9)/L was 23 days in the GM-CSF group versus 25 days in the control group (P = . 0002) with the percentages of patients who recovered being 81% and 71% , respectively. With a median follow-up of 36 months, the probabilitie s of survival at 2 years after randomization were estimated at 22% for individuals assigned to the GM-CSF treatment as well as for control p atients (P = .55). Disease-free survival at 2 years compared 15% and 1 9% for the two treatment groups (P = .69). The number of nights spent in the hospital, number of transfusions, and frequencies and types of hemorrhages and infections did not differ either. The cytogenetic resu lts at diagnosis of this study in elderly AML shows that there is a re latively high numerical representation of patients with abnormal cytog enetics (55% of documented cases), who showed significantly inferior r esponse rates and survival duration. We conclude that, except for a fa ster neutrophil recovery, GM-CSF during and after induction chemothera py does not improve the clinical outcome of elderly patients with AML. (C) 1997 by The American Society of Hematology.