Impact of HLA Mismatch on the Incidence of Acute GVHD and Rejection after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation (RICT).

HLA incompatibility between the donor and recipient is the most critical factor governing the incidence of rejection and GVHD after conventional allogeneic stem cell transplantation. But the impact of HLA disparity on GVHD and graft rejection after RICT remains to be elucidated. We retrospectively analyzed the outcomes of 437 patients who underwent bone marrow (n=95) or peripheral blood stem cell RICT (n=342). The numbers of patients who received a graft from a HLA-matched (275 from siblings, 11 from family members, and 54 from unrelated donors), one-locus-mismatched, 2- or 3-loci-mismatched donor were 340, 65, and 32, respectively. The HLA-matched group included significantly higher population of patients who received cyclosporine alone for GVHD prophylaxis. The overall cumulative incidence of grade II-IV acute GVHD was 40% for all subjects. It was 38% (95% CI; 33%–43%) in recipients of HLA-matched donors, 43% (95% CI; 31%–54%) in those of one-locus-mismatched donors, and 54% (95% CI; 37%–68%) in those of 2–3-loci-mismatched donors. A Cox regression model adjusted for potential confounders including GVHD prophylaxis demonstrated that 2-3 loci-mismatch was identified as an independent risk factor of grade II-IV acute GVHD (Table). Use of antithymocyte globulin was identified as an independent better protective factor for GVHD (HR;0.66, p=.003). Cumulative incidence of rejection was significantly higher after one-locus mismatch RICT (Table) and the risk tended to increase in relation to an increase of HLA disparity. Malignant disease was identified as an independent prognostic factor for rejection. In patients with hematologic malignancies, overall survival (OS) of recipients of 2–3-loci-mismatched RICT at 1 year (38%, 95%CI; 21%–54%) was significantly worse than that after HLA-matched RICT (65%, 95%CI; 59%–70%). By contrast, there was no statistical difference in the incidence of grade II-IV acute GVHD and OS between HLA-matched RICT and one-locus-mismatched RICT. Multivariate analysis demonstrated 2–3-loci-mismatch (Table) and high-risk disease (HR; 2.3, p=.001) as independent risk factors for OS. Thus, HLA incompatibility between the donor and recipient is an important risk factor for rejection, acute GVHD and overall survival after RICT. Therefore RICT from a one-locus-mismatched donor may represent an effective alternative approach in patients lacking HLA-matched sibling donors.