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.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Ringdén
Olle
O
Centre for Allogeneic Stem Cell Transplantation, Division of Clinical Immunology F79, Karolinska Institute, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. Olle.Ringden@labmed.ki.se
Labopin
Myriam
M
Gorin
Norbert-Claude
NC
Le Blanc
Katarina
K
Rocha
Vanderson
V
Gluckman
Eliane
E
Reiffers
Jules
J
Arcese
William
W
Vossen
Jaak M
JM
Jouet
Jean-Pierre
JP
Cordonnier
Catherine
C
Frassoni
Francesco
F
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects* / Q000627:therapeutic use; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007223:Infant; D015479:Leukemia, Myelomonocytic, Acute / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000601:surgery*; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D006680:HLA Antigens; D016179:Granulocyte Colony-Stimulating Factor