A randomized study of granulocyte colony-stimulating factor applied duringand after chemotherapy in patients with poor risk myelodysplastic syndromes: a report from the HOVON Cooperative Group

The purpose of this study was to determine the safety and efficacy of filgr astim as an adjunct to induction and consolidation chemotherapy in poor ris k patients with myelodysplastic syndrome (MDS). Filgrastim was given both d uring and after chemotherapy with the objective to accelerate hematopoietic repopulation and enhance the efficacy of chemotherapy. In a prospective ra ndomized multicentre phase II trial, a total of 64 patients with poor risk primary MDS were randomized to receive either granulocyte colony-stimulatin g factor (G-CSF, filgrastim, AMGEN, Breda, The Netherlands) 5 mu g/kg/day s ubcutaneously or no G-CSF in addition to daunomycin (30 mg/m(2)/days 1, 2 a nd 3 intravenous bolus) and cytarabine (200 mg/m(2) days 1-7, continuous in fusion). The overall complete response rate was 63%: 73% for patients recei ving filgrastim as compared to 52% in the standard arm (P = 0.08). Overall survival at 2 years was estimated at 29% for patients assigned to the filgr astim arm and 16% for control patients (P = 0.22). The median time for reco very of granulocytes towards 1.0x10(9)/I post-chemotherapy was 23 days in t he filgrastim-treated patients vs 35 days in the standard arm (P = 0.015). There were no differences in time of platelet recovery, length of hospital stay, duration of antibiotic use or infectious complications between the tw o treatment groups. However the earlier recovery of neutrophils in the filg rastim group was associated with a reduced interval of 9 days between the i nduction and consolidation cycle. In patients with poor risk MDS the use of filgrastim during and after induction therapy results in a significantly r educed neutrophil recovery time. Further study may be warranted to see if t he apparent trend of the improved response to chemotherapy in combination w ith filgrastim can be confirmed in greater number of patients and to assess the effect of the addition of filgrastim on survival.