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

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.

SUBMITTER: Madbouly A 

PROVIDER: S-EPMC5541944 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature