Filgrastim following HLA-Identical Allogeneic Bone Marrow Transplantation: Long-Term Outcomes of a Randomized Trial

Abstract

Human recombinant granulocyte colony stimulating factor reduces the duration of neutropenia following HLA-identical allogeneic bone marrow transplantation. However, its use remains controversial due to the risk of increasing the incidence of acute graft-versus-host disease (GVHD) and slower platelet recovery. To clarify these risks, we conducted a prospective randomized placebo-controlled trial of filgrastim 5 µg/kg/day i.v. from day 7 post-transplant until neutrophil recovery in 145 consecutive adults undergoing HLA-identical allogeneic bone marrow transplantation, with cyclosporine and methotrexate as GVHD prophylaxis. The primary endpoint was the incidence of acute GVHD; hematological recovery, nonrelapse mortality, and post-transplant complications were secondary endpoints. Filgrastim had no significant effect on the incidence of acute GVHD, platelet recovery, platelet transfusion requirements, chronic GVHD, or survival. Filgrastim accelerated granulocyte recovery significantly (with absolute neutrophil counts >.5 × 109/L achieved after a median of 16 days versus 23 days for placebo; P < .0001), and reduced both early nonrelapse mortality (2.9% versus 10.5%; P = .042) and the duration of i.v. antibiotic therapy (18 days versus 26 days; P = .001) and hospitalization (27 versus 34 days; P = .017). In conclusion, in this setting, filgrastim reduced significantly the duration of neutropenia, i.v. antibiotic therapy, hospitalization, and early nonrelapse mortality, without increasing the risk of acute and chronic GVHD or relapse, or delaying platelet recovery.