Clinical significance of HLA-E*0103 homozygosity on survival after allogeneic hematopoietic stem-cell transplantation

Transplantation. 2009 Aug 27;88(4):528-32. doi: 10.1097/TP.0b013e3181b0e79e.

Abstract

Background: Hematopoietic stem-cell transplantation is a well-established treatment in various hematologic malignancies, but the outcome depends on disease relapse, infections, and the development and severity of acute and chronic graft-versus-host disease. Some evidence has revealed an important role for the nonclassical major histocompatibility complex class I molecules in transplantation, most notably human leukocyte antigen (HLA)-E. This study evaluates the impact of HLA-E alleles on transplantation outcome after HLA-matched allogeneic HSCT.

Methods: We genotyped DNA for HLA-E polymorphism from 83 recipients and their respective donors by real-time polymerase chain reaction after melting curve analysis and compared the results with clinical outcome.

Results: HLA-E*0103 homozygous patients showed a higher probability of overall survival (P=0.003) and disease-free survival (P=0.001) in a univariate model. Cox regression analysis confirmed HLA-E*0103, 0103 (P=0.006; relative risk 1.12; 95% confidence interval 0.31-1.94) and early stage of disease (P=0.005; relative risk 1.16; 95% confidence interval 0.45-1.86) as independent factors improving overall survival. Moreover, homozygosity for HLA-E*0103 was associated with a significant decreased incidence of transplant-related mortality (P=0.01).

Conclusions: We found an association between HLA-E*0103 homozygosity and the significant reduction of transplant-related mortality in related and unrelated HSCT. The risk of posttransplant complications was significantly reduced when the donor possesses the HLA-E*0103, 0103 genotype, and this was translated in a better overall survival.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Base Sequence
  • Cohort Studies
  • DNA Primers / genetics
  • Female
  • Genotype
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • HLA Antigens / genetics*
  • HLA-E Antigens
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Heterozygote
  • Histocompatibility Antigens Class I
  • Homozygote
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Transplantation, Homologous
  • Young Adult

Substances

  • DNA Primers
  • HLA Antigens
  • Histocompatibility Antigens Class I