Changes in the clinical impact of high-risk human leukocyte antigen allele mismatch combinations on the outcome of unrelated bone marrow transplantation

Biol Blood Marrow Transplant. 2014 Apr;20(4):526-35. doi: 10.1016/j.bbmt.2014.01.003. Epub 2014 Jan 10.

Abstract

Several high-risk HLA allele mismatch combinations (HR-MMs) for severe acute graft-versus-host disease (GVHD) have been identified by analyzing transplantation outcomes in Japanese unrelated hematopoietic stem cell transplant recipients. In this study, we analyzed the effects of HR-MMs in 3 transplantation time periods. We confirmed that the incidence of grade III to IV acute GVHD in the HR-MM group was significantly higher than that in the low-risk (LR) MM group (hazard ratio [HR], 2.74; P < .0001) in the early time period (1993 to 2001). However, the difference in the incidence of grade III to IV acute GVHD between the HR-MM and LR-MM groups was not statistically significant (HR, 1.06; P = .85 and HR, .40; P = .21, respectively) in the mid (2002 to 2007) and late (2008 to 2011) time periods. Similarly, survival in the HR-MM group was significantly inferior to that in the LR-MM group (HR, 1.46; P = .019) in the early time period, whereas the difference in survival between the 2 groups was not statistically significant in the mid and late time periods (HR, 1.06; P = .75 and HR, .82; P = .58, respectively). In conclusion, the adverse impact of HR-MM has become less significant over time. Unrelated transplantation with a single HR-MM could be a viable option in the absence of a matched unrelated donor or an unrelated donor with a single LR-MM.

Keywords: Bone marrow transplantation; Graft-versus-host disease; Human leukocyte antigens; Leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Alleles*
  • Female
  • Gene Expression
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / therapy*
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Male
  • Risk
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors

Substances

  • HLA Antigens