Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction

• Published in: Blood 2006-04, Vol.107 (7), p.2984-2992
• Main Authors: Fleischhauer, Katharina, Locatelli, Franco, Zecca, Marco, Orofino, Maria Grazia, Giardini, Claudio, De Stefano, Piero, Pession, Andrea, Iannone, Angela Maria, Carcassi, Carlo, Zino, Elisabetta, La Nasa, Giorgio
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemias. Hemoglobinopathies; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Child; Diseases of red blood cells; Female; Graft Rejection - immunology; Graft vs Host Reaction - immunology; Hematologic and hematopoietic diseases; Histocompatibility Testing; HLA-DP Antigens - immunology; HLA-DP beta-Chains; Host vs Graft Reaction - immunology; Humans; Male; Medical sciences; Retrospective Studies; Stem Cell Transplantation - adverse effects; Thalassemia - immunology; Thalassemia - therapy; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Homologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-08-3374

The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for β-thalassemia may be hampered by the occurrence of graft rejection. Here, we show that the rate of this complication can be reduced by selecting 5-loci HLA-matched donors without nonpermissive mismatches at HLA-DPB1, defined according to an algorithm previously described and based on principles of central T-cell tolerance. Seventy-two consecutive patients and their UDs, prospectively selected for matching at the allelic level for HLA-A, -B, -C, -DRB, and -DQB1 loci, were enrolled in the analysis. These pairs were either DPB1 matched/permissively mismatched (n = 45, control group) or had at least one nonpermissive DPB1 mismatch in the host-versus-graft (HvG; n = 17) or in the graft-versus-host (GvH; n = 10) direction. In multivariate analysis, the risk of rejection was significantly increased in the group with HvG disparity (RR = 7.42; 95% CI = 1.29-42.68; P = .02) as compared to the control group. A lower, statistically significant, probability of thalassemia-free survival was found in patients belonging to the HvG group as compared to controls (RR = 5.15; 95% CI = 1.58-16.82; P = .01). These data suggest that in patients with thalassemia, the incidence of graft failure after HSCT may be reduced by appropriate selection of UDs, with such selection taking into account the functional rules of immunogenetics.