Originally published as JCO Early Release 10.1200/JCO.2004.06.102 on December 22 2003

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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

From the Centre for Allogeneic Stem-Cell Transplantation and Division of Clinical Immunology, Huddinge University Hospital, Stockholm, Sweden; BA1638 Université Pierre et Marie Curie and Centre Claude Bernard, Centre International Greffes, Hôpital Saint-Antoine and European Group for Blood and Marrow Transplantation Data Center, Institut des Cordeliers; Hôpital Saint-Louis, Paris; Hôpital de Haut-Levèque, Pessac; Service des Maladie du Sang, Lille; Hôpital Henri Mondor, Creteil, France; University La Sapienza, Rome; Ospedale San Martino, Genova, Italy; and Bone Marrow Transplantation Centre, Leiden, the Netherlands.

Address reprint requests to Olle Ringdén, MD, PhD, Karolinska Institute, Huddinge University Hospital, Centre for Allogeneic Stem Cell Transplantation, Division of Clinical Immunology, F79, SE-141 86 Stockholm, Sweden; e-mail: Olle.Ringden{at}labmed.ki.se

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

Supported by European Group for Blood and Marrow Transplantation funds and by convention 6113 from the Association pour la Recherche contre le Cancer, Villejuif, France, and grant BMH1-CT-94-0300 from the European Community. O.R. was supported by grants from the Swedish Cancer Society (0070-B99-13XAC), the Children's Cancer Foundation (2000/067), the Swedish Medical Research Council (K2000-06X-05971-20A), the Cancer Society in Stockholm, the Tobias Foundation, and Karolinska Institute.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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Related Editorial

• Use of Granulocyte Colony-Stimulating Factor Following Hematopoietic Cell Transplantation: Does Haste Make Waste?
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  JCO 2004 22: 390-391 [Full Text]

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• Myeloid Growth Factors Should Not Be Administered Routinely After Allogeneic Hematopoietic Stem-Cell Transplantation
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• In Reply:
  Olle Ringdén
  JCO 2004 22: 4430-4432 [Full Text]

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