Sex-specific survival difference in association with HLA-DRB1∗04 following allogeneic haematopoietic stem cell transplantation for lymphoid malignancies

Hum Immunol. 2018 Jan;79(1):13-19. doi: 10.1016/j.humimm.2017.10.010. Epub 2017 Oct 31.

Abstract

The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1∗04 carriers compared with non-carriers (p = 0.01). Survival benefit was confined to male patients (in multivariate analyses p = 0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p = 0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1∗04 carrier donors resulted in superior survival compared with female non-carrier donors (p = 0.01). Combined analyses including recipient/donor gender and HLA-DRB1∗04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1∗04 carriership (p = 0.04) with best survival among HLA-DRB1∗04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1∗04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1∗04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1∗04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors.

Keywords: Allogeneic HSCT; HLA allele groups; HLA-DRB1∗04; Lymphoid malignancy; Survival.

MeSH terms

  • Adult
  • Cohort Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype*
  • HLA-A Antigens / genetics*
  • HLA-B Antigens / genetics*
  • HLA-DRB1 Chains / genetics*
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Hungary
  • Leukemia, Lymphoid / genetics*
  • Leukemia, Lymphoid / mortality
  • Leukemia, Lymphoid / therapy
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / therapy
  • Polymorphism, Genetic
  • Prognosis
  • Retrospective Studies
  • Sex Factors
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DRB1 Chains