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

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. Patients and 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. (c) 2006 International Society for Experimental Hematology.