Investigating the Association of Genetic Admixture and Donor/Recipient Genetic Disparity with Transplant Outcomes

Biol Blood Marrow Transplant. 2017 Jun;23(6):1029-1037. doi: 10.1016/j.bbmt.2017.02.019. Epub 2017 Mar 2.

Abstract

Disparities in survival after allogeneic hematopoietic cell transplantation have been reported for some race and ethnic groups, despite comparable HLA matching. Individuals' ethnic and race groups, as reported through self-identification, can change over time because of multiple sociological factors. We studied the effect of 2 measures of genetic similarity in 1378 recipients who underwent myeloablative first allogeneic hematopoietic cell transplantation between 1995 and 2011 and their unrelated 10 of 10 HLA-A, -B, -C, -DRB1, and-DQB1- matched donors. The studied factors were as follows (1) donor and recipient genetic ancestral admixture and (2) pairwise donor/recipient genetic distance. Increased African genetic admixture for either transplant recipients or donors was associated with increased risk of overall mortality (hazard ratio [HR], 2.26; P = .005 and HR, 3.09; P = .0002, respectively) and transplant-related mortality (HR, 3.3; P = .0003 and HR, 3.86; P = .0001, respectively) and decreased disease-free survival (HR, 1.9; P = .02 and HR, 2.46; P = .002 respectively). The observed effect, albeit statistically significant, was relevant to a small subset of the studied population and was notably correlated with self-reported African-American race. We were not able to control for other nongenetic factors, such as access to health care or other socioeconomic factors; however, the results suggest the influence of a genetic driver. Our findings confirm what has been previously reported for African-American recipients and show similar results for donors. No significant association was found with donor/recipient genetic distance.

Keywords: African-American race; Ancestry informative markers; Genetic admixture; Genetic ancestry; Hematopoietic stem cell transplantation; Race and ethnicity.

MeSH terms

  • Adult
  • Female
  • Genetic Variation*
  • Healthcare Disparities / ethnology*
  • Hematopoietic Stem Cell Transplantation / ethnology*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Male
  • Middle Aged
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors*
  • Young Adult