title: Evidence that donor intrinsic response to G-CSF is the best predictor of acute graft-vs-host disease following allogeneic peripheral blood stem cell transplantation.
abstract: OBJECTIVE
  Risk factors of acute graft-vs-host disease (GVHD) following allogeneic bone marrow transplantation have been well described before. In this study, we tested the hypothesis that acute GVHD after allogeneic peripheral blood stem cell (PBSC) transplant might be associated with donors' responsiveness to granulocyte colony-stimulating factor (G-CSF), rather than the dose of CD34(+) cells infused.
  
  
  METHODS
  We retrospectively analyzed mobilization and transplant data (demographic characteristics, donor blood cell subsets after G-CSF, graft composition) in 149 consecutive HLA-identical donor/recipient pairs in order to identify acute GVHD risk factors.
  
  
  RESULTS
  In 25% of donors, G-CSF mobilization led to an outstanding response, defined as greater than 117 x 10(6) CD34(+) cells/L. Overall, incidence of grades II-IV acute GVHD was 20.1% (95% CI: 16.6-23.6). Following univariate analysis, the incidence increased significantly in recipients receiving greater than 10 x 10(6) CD34(+) cells/kg (35% vs 15%; p = 0.007), and those transplanted from outstanding mobilizers (41% vs 12%, p < 0.0001). In multivariate analysis, only transplantation from outstanding mobilizers remained significant (p = 0.02). Donor or recipient demographic characteristics and lymphocyte subsets reinfused in the graft had no impact.
  
  
  CONCLUSIONS
  We demonstrate for the first time that donor responsiveness to G-CSF is associated with acute GVHD following PBSC transplantation. If confirmed, this correlation will help to identify recipients who could potentially benefit from improved prophylaxis. As further corollary, decreasing the dose of CD34(+) cells infused is unlikely to prevent acute GVHD. Future studies should focus on the molecular bases of interindividual discrepancies in response to G-CSF.
authors.affiliation: Division of Hematology, Hôpital Maisonneuve-Rosemont, and Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhédin
authors.forename: Inès
authors.initials: I
authors.lastname: Chamakhi
authors.forename: Claude
authors.initials: C
authors.lastname: Perreault
authors.forename: Denis-Claude
authors.initials: DC
authors.lastname: Roy
authors.forename: Guy
authors.initials: G
authors.lastname: Sauvageau
authors.forename: Thierry
authors.initials: T
authors.lastname: Ducruet
authors.forename: Lambert
authors.initials: L
authors.lastname: Busque
authors.forename: Douglas
authors.initials: D
authors.lastname: Fish
authors.forename: Robert
authors.initials: R
authors.lastname: Bélanger
authors.forename: Jean
authors.initials: J
authors.lastname: Roy
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D019072:Antibiotic Prophylaxis; D018952:Antigens, CD34 / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D008727:Methotrexate