GM-CSF IN A DOUBLE-BLIND RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN THERAPY OF ADULT PATIENTS WITH DE-NOVO ACUTE MYELOID-LEUKEMIA (AML)

We investigated whether GM-CSF given concomitantly with chemotherapy ( CT) and thereafter, improves the outcome of adults with de novo AML by increasing the efficacy of CT and reducing infections. CT included Ar a-C, daunorubicin and etoposide (DAV) for induction and early consolid ation therapy and one cycle with high-dose (patients aged less than or equal to 50 years) or intermediate dose Ara-C (patients aged >50 year s)/daunorubicin for late consolidation therapy. Eighty patients were r andomized after DAVI to receive either GM-CSF (E. coli, 250 mu g/m(2)/ day, s.c.) or placebo starting 48 h prior to DAVII and the subsequent courses and given throughout CT until the absolute neutrophil count ha d recovered to >500/mu l. The CR rate was 81% in the GM-CSF and 79% in the placebo group (p = 0.57; Fisher's exact test). The probability of relapse-free survival at 41 months after a median follow-up of 35 mon ths was 42% in the GM-CSF and 41% in the placebo group (p = 0.89; log rank test). GM-CSF did not shorten the period of neutropenia less than or equal to 500/mu l, while it prolonged the duration of thrombocytop enia less than or equal to 25 000/mu l. The incidence and severity of infections as well as the non-hematological toxicity were similar in: both groups. In summary, in this randomized trial GM-CSF as an adjunct to AML therapy was feasible. For the present GM-CSF does not have a s ignificant effect on treatment outcome.