title: 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.
authors.affiliation: National Marrow Donor Program/Be The Match, Minneapolis, Minnesota. Electronic address: amadboul@nmdp.org.
authors.forename: Abeer
authors.initials: A
authors.lastname: Madbouly
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.affiliation: National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
authors.forename: Vanja
authors.initials: V
authors.lastname: Paunic
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Vierra-Green
authors.affiliation: Institute for Experimental Cellular Therapy, University Hospital, Essen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Hsu
authors.affiliation: University of Colorado-Denver, Denver, Colorado.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Navneet S
authors.initials: NS
authors.lastname: Majhail
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin; Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.affiliation: National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
authors.forename: Martin
authors.initials: M
authors.lastname: Maiers
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation; D054625:Healthcare Disparities / Q000208:ethnology*; D018380:Hematopoietic Stem Cell Transplantation / Q000208:ethnology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
keywords: African-American race; Ancestry informative markers; Genetic admixture; Genetic ancestry; Hematopoietic stem cell transplantation; Race and ethnicity