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

Abeer Madbouly, Tao Wang, Michael Haagenson, Vanja Paunic, Cynthia Vierra-Green, Katharina Fleischhauer, Katharine C. Hsu, Michael R. Verneris, Navneet S. Majhail, Stephanie J. Lee, Stephen R. Spellman, Martin Maiers

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1029-1037
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number6
DOIs
StatePublished - Jun 2017

Bibliographical note

Funding Information:
We would like to acknowledge Mark Albrecht for his valuable input on some analysis aspects and Heather Severance for helping with the submission process. This work was supported by the Office of Naval Research grant N00014-11-1-0339. The CIBMTR is supported by Public Health Service grant/cooperative agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-15-1-0848 and N00014-16-1-2020 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Inc.; Alexion; *Amgen Inc.; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; Be The Match Foundation; *Bluebird Bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cellular Dynamics International, Inc.; Cerus Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics; Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children's Foundation; Leukemia and Lymphoma Society; Medac, GmbH; MedImmune; Medical College of Wisconsin; *Merck & Co., Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; *Miltenyi Biotec; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co., Ltd.?Japan; PCORI; Perkin Elmer, Inc.; Pfizer Inc.; *Sanofi US; *Seattle Genetics; *Spectrum Pharmaceuticals; St. Baldrick's Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; University of Minnesota; and *WellPoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA), or any other agency of the US government.

Keywords

  • African-American race
  • Ancestry informative markers
  • Genetic admixture
  • Genetic ancestry
  • Hematopoietic stem cell transplantation
  • Race and ethnicity

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