Results of a randomized double-blind placebo-controlled trial evaluating sequential high-dose cytosine arabinoside mitoxantrone chemotherapy with or without granulocyte/macrophage-colony-stimulating factor in high-risk myelodysplastic syndromes

A prospective, randomized, double-blind placebo-controlled trial was design ed to evaluate the impact of granulocyte/macrophage-colony-stimulating fact or (GM-CSF) on the efficacy of sequential high-dose cytosine arabinoside/mi toxantrone chemotherapy (S-HAM) in adult patients with high-risk myelodyspl astic syndromes (MDS). GM-CSF or placebo was given subcutaneously once dail y at a dose of 250 mu g/m(2), starting 48 h prior to chemotherapy, and cont inued until neutrophil recovery. Owing to high toxicity and slow patient re cruitement the study was closed and unblinded after 31 patients had been en rolled; 15 were randomized to receive placebo and 16 to receive GM-CSF. A t otal of 29 patients were evaluable for response; their median age was 57 ye ars. Ten patients achieved a complete remission (34.5%), 9 patients had per sistent MDS (31%), 10 patients died within 6 weeks after the onset of treat ment (early death) (34.5%). The median remission duration was 190 days (ran ge: 2.5-45 months). Among the 29 evaluable patients no significant differen ces could be found between the two study arms regarding complete remission rate [GM-CSF: 31% (5/16) versus placebo: 38% (5/13) P = 0.45], rate of pers istent MDS [GM-CSF: 25% (4/16) versus 38% (5/13) P = 0.35), early death rat e [44% (7/16) versus 23% (3/13) P = 0.22] and remission duration (GMCSF: 87 days versus placebo 221 days). Duration of granulocytopenia (median: 33 da ys with GM-CSF) versus 35 days with placebo) and frequency of infectious ep isodes were not significantly influenced by GMCSF. The small number of pati ents finally analyzed means that no definite conclusions about the effect o f GM-CSF can be reached.