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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2984-2992. Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-08-3374.
TRANSPLANTATION Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft directionFrom the HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Scientifico H. S. Raffaele, Milan; Pediatric Hematology-Oncology, IRCCS Policlinico S. Matteo, Pavia; Department of Biomedical and Biotechnological Sciences, Bone Marrow Transplantation Unit, University of Cagliari; Department of Hematology, Bone Marrow Transplantation Unit of Muraglia, Ospedale San Salvatore, Pesaro; Department of Pediatrics, University of Bologna, Ospedale S. Orsola-Malpighi, Bologna; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, IRCCS Policlinico S. Matteo, Pavia; Department of Medical Genetics, University of Cagliari; and Bone Marrow Transplantation Unit, Ospedale Binaghi, Cagliari, Italy.
The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for
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| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
-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. 
