Long-Term Safety of GM-CSF (Molgramostim) Administration After Allogeneic Bone Marrow Transplantation for Hematologic Malignancies: Five-Year Follow-Up of a Double-Blind Randomized Placebo-Controlled Study

In a double-blind, randomized study performed between 1988 and 1990,40 patients undergoing allogeneic BMT from HLA-identical siblings for hematologic malignancies received 8 mg/kg/d rHuGM-CSF (molgramostim, n = 20) or placebo (n = 20) for 14 days. The median neutrophil count on day 14 was significantly higher in the GM-CSF group (1.90 vs 0.46 10⁹/L, P<. 0001). The incidence of acute GVHD and transplant-related mortality were comparable. Only two deaths occurred after 6 months; one due to pulmonary fibrosis in the GM-CSF group on day 1591, and one due to relapse on day 1590 in the placebo group. The Karnofsky score of the 10 survivors, 3 in the placebo group and 7 in the GM-CSF group, is 90-100% (median 100%), and none has chronic GVHD requiring therapy. There was no evidence of increased relapse in the GM-CSF group with only two relapses occumng; both in the placebo group. With a follow-up of 4.5-6.8 years (median 5.5 years), these patients are amongst the longest surviving patients to have received a recombinant growth factor post-allo-graft. We conclude that the administration of GM-CSF after allogeneic BMT does not appear to be associated with an increased incidence of chronic GVHD or relapse, or of other adverse effects such as the development of myelodysplasia.