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

J Clin Oncol. 2004 Feb 1;22(3):416-23. doi: 10.1200/JCO.2004.06.102. Epub 2003 Dec 22.

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 x 10(9)/L (P <.01), but platelet engraftment ( > 50 x 10(9)/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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow Transplantation*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Graft Survival
  • Graft vs Host Disease / etiology*
  • Granulocyte Colony-Stimulating Factor / adverse effects*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • HLA Antigens / metabolism
  • Humans
  • Infant
  • Leukemia, Myelomonocytic, Acute / mortality
  • Leukemia, Myelomonocytic, Acute / surgery*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neutrophils / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / surgery*
  • Risk Factors
  • Survival Rate
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • HLA Antigens
  • Granulocyte Colony-Stimulating Factor