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Biol Blood Marrow Transplant. 2013 Feb;19(2):274-82. doi: 10.1016/j.bbmt.2012.09.008. Epub 2012 Sep 27.

Association of disparities in known minor histocompatibility antigens with relapse-free survival and graft-versus-host disease after allogeneic stem cell transplantation.

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  • 1Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

Allogeneic stem cell transplantation (allo-SCT) can induce remission in patients with hematologic malignancies due to graft-versus-tumor (GVT) responses. This immune-mediated antitumor effect is often accompanied by detrimental graft-versus-host disease (GVHD), however. Both GVT and GVHD are mediated by minor histocompatibility antigen (MiHA)-specific T cells recognizing peptide products from polymorphic genes that differ between recipient and donor. In this study, we evaluated whether mismatches in a panel of 17 MiHAs are associated with clinical outcome after partially T cell-depleted allo-SCT. Comprehensive statistical analysis revealed that DNA mismatches for one or more autosomal-encoded MiHAs was associated with increased relapse-free survival in recipients of sibling transplants (P = .04), particularly in those with multiple myeloma (P = .02). Moreover, mismatches for the ubiquitous Y chromosome-derived MiHAs resulted in a higher incidence of acute GVHD grade III-IV (P = .004), whereas autosomal MiHA mismatches, ubiquitous or restricted to hematopoietic cells, were not associated with severe GVHD. Finally, we found considerable differences among MiHAs in their capability of inducing in vivo T cell responses using dual-color tetramer analysis of peripheral blood samples collected after allo-SCT. Importantly, detection of MiHA-specific T cell responses was associated with improved relapse-free survival in recipients of sibling transplants (P = .01). Our findings provide a rationale for further boosting GVT immunity toward autosomal MiHAs with a hematopoietic restriction to improve outcomes after HLA-matched allo-SCT.

Copyright © 2013 American Society for Blood and Marrow Transplantation. All rights reserved.

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PMID:
23022467
[PubMed - indexed for MEDLINE]
PMCID:
PMC3553241
Free PMC Article

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