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

Publication Type:

Journal Article

Source:

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (2017)

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 due to multiple sociological factors. We studied the effect of two measures of genetic similarity in 1,378 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: i) Donor and recipient genetic ancestral admixture, and ii) Pairwise donor/recipient genetic distance. Increased African genetic admixture for either transplant recipients or donors was associated with increased risk of overall mortality (HR=2.26, p=0.005 and HR=3.09, p=0.0002 respectively), Transplant Related Mortality (HR=3.3, p=0.0003 and HR=3.86, p=0.0001 respectively) and decreased Disease Free Survival (HR=1.9, p=0.02 and HR=2.46, p=0.002 respectively). The observed effect, albeit statistically significant, was relevant to small subset of the studied population and was notably correlated with self-reported African-American race. We were not able to control for other non-genetic factors such as access to healthcare or other socio-economic 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.