Treatment With Granulocyte Colony-Stimulating Factor After Allogeneic Bone Marrow Transplantation for Acute Leukemia Increases the Risk of Graft-Versus-Host Disease and Death: A Study From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

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Abstract
Purpose: Granulocyte colony-stimulating factor (G-CSF) is given after bone marrow transplantation (BMT) to shorten the neutropenic phase. Its effects have not been evaluated in a large patient population. Patients and Methods: We studied 1,789 patients with acute leukemia receiving BMT and 434 patients receiving peripheral-blood stem cells (PBSCs) from HLA-identical siblings from 1992 to 2002 and reported the findings to the European Group for Blood and Marrow Transplantation. Among the BMT and PBSC patients, 501 (28%) and 175 (40%), respectively, were treated with G-CSF during the first 14 days after the transplantation. The outcome variables were entered into a Cox proportional hazards model. Results: BMT and PBSC patients treated with G-CSF had a faster engraftment of absolute neutrophils greater than 0.5 × 109/L (P < .01), but platelet engraftment ( > 50 × 109/L) was slower (P < .001). In the BMT patients, acute graft-versus-host disease (GVHD) grades II to IV was 50% ± 5% (± 95% CI) in the G-CSF group versus 39% ± 3% in the controls (relative risk [RR], 1.33; P = .007, in the multivariate analysis). The incidence of chronic GVHD was also increased (RR, 1.29; P = .03). G-CSF was associated with an increase in transplantation-related mortality (TRM; RR, 1.73; P = .00016) and had no effect on relapse but reduced survival (RR, 0.59; P < .0001) and leukemia-free survival rates (LFS; RR, 0.64; P = .0003). No such effects of G-CSF were seen in patients receiving PBSC. Conclusion: After BMT, platelet engraftment was delayed, and GVHD and TRM were increased. Survival and LFS were reduced. This suggests that G-CSF should not be given shortly after BMT.

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