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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Graft Survival / immunology*
  • Graft vs Host Disease / immunology*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / surgery*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Middle Aged
  • Recurrence
  • Retrospective Studies
  • Transplantation, Homologous
  • Young Adult