TY - JOUR
T1 - Investigating the Association of Genetic Admixture and Donor/Recipient Genetic Disparity with Transplant Outcomes
AU - Madbouly, Abeer
AU - Wang, Tao
AU - Haagenson, Michael
AU - Paunic, Vanja
AU - Vierra-Green, Cynthia
AU - Fleischhauer, Katharina
AU - Hsu, Katharine C.
AU - Verneris, Michael R.
AU - Majhail, Navneet S.
AU - Lee, Stephanie J.
AU - Spellman, Stephen R.
AU - Maiers, Martin
N1 - Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - African-American race
KW - Ancestry informative markers
KW - Genetic admixture
KW - Genetic ancestry
KW - Hematopoietic stem cell transplantation
KW - Race and ethnicity
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U2 - 10.1016/j.bbmt.2017.02.019
DO - 10.1016/j.bbmt.2017.02.019
M3 - Article
C2 - 28263917
AN - SCOPUS:85017554048
SN - 1083-8791
VL - 23
SP - 1029
EP - 1037
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -