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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2851-2858. Prepublished online as a Blood First Edition Paper on November 7, 2008; DOI 10.1182/blood-2008-08-171934. This Article Full Text Full Text (PDF) Supplemental Appendix and Tables All Versions of this Article: blood-2008-08-171934v1 113/12/2851    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kawase, T. Articles by Morishima, Y. Search for Related Content PubMed PubMed Citation Articles by Kawase, T. Articles by Morishima, Y. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism Takakazu Kawase1, Keitaro Matsuo1, Koichi Kashiwase2, Hidetoshi Inoko3, Hiroh Saji4, Seishi Ogawa5, Shunichi Kato6, Takehiko Sasazuki7, Yoshihisa Kodera8, Yasuo Morishima9, for The Japan Marrow Donor Program 1 Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya; 2 Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo; 3 Division of Molecular Science, Tokai University School of Medicine, Isehara; 4 HLA Laboratory, NPO, Kyoto; 5 The 21st Century COE Program, Graduate School of Medicine, University of Tokyo, Tokyo; 6 Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara; 7 International Medical Center of Japan, Tokyo; 8 Japanese Red Cross Nagoya First Hospital, Nagoya; and 9 Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan The finding that the risk of relapse in hematologic malignancy decreases after allogeneic hematopoietic stem cell transplantation (HSCT) has lead to the concept of a graft-versus-leukemia (GVL) effect. However, this beneficial effect is considered to be frequently offset by graft-versus-host disease (GVHD). Thus, improving HSCT outcomes by separating GVL from GVHD is a key clinical issue. This cohort study registered 4643 patients with hematologic malignancies who received transplants from unrelated donors. Six major human leukocyte antigen (HLA) loci were retrospectively genotyped. We identified 4 HLA-Cw and 6 HLA-DPB1 mismatch combinations responsible for a decreased risk of relapse; of these, 8 of 10 combinations were different from those responsible for severe acute GVHD, including all 6 of the HLA-DPB1 combinations. Pairs with these combinations of HLA-DPB1 were associated with a significantly better overall survival than were completely matched pairs. Moreover, several amino acid substitutions on specific positions responsible for a decreased risk of relapse were identified in HLA-Cw, but not in HLA-DPB1. These findings might be crucial to elucidating the mechanism of the decreased risk of relapse on the basis of HLA molecule. Donor selection made in consideration of these results might allow the separation of GVL from acute GVHD, especially in HLA-DPB1 mismatch combinations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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