1. Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study.
- Author
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Mayor NP, Hayhurst JD, Turner TR, Szydlo RM, Shaw BE, Bultitude WP, Sayno JR, Tavarozzi F, Latham K, Anthias C, Robinson J, Braund H, Danby R, Perry J, Wilson MC, Bloor AJ, McQuaker IG, MacKinnon S, Marks DI, Pagliuca A, Potter MN, Potter VT, Russell NH, Thomson KJ, Madrigal JA, and Marsh SGE
- Subjects
- Adult, Alleles, Female, Hematopoietic Stem Cell Transplantation methods, Histocompatibility genetics, Histocompatibility Testing methods, Humans, Male, Middle Aged, Retrospective Studies, Survival Analysis, Unrelated Donors, Hematopoietic Stem Cell Transplantation mortality, Histocompatibility immunology, Histocompatibility Testing standards, Sequence Analysis, DNA standards
- Abstract
HLA matching at an allelic-level resolution for volunteer unrelated donor (VUD) hematopoietic cell transplantation (HCT) results in improved survival and fewer post-transplant complications. Limitations in typing technologies used for the hyperpolymorphic HLA genes have meant that variations outside of the antigen recognition domain (ARD) have not been previously characterized in HCT. Our aim was to explore the extent of diversity outside of the ARD and determine the impact of this diversity on transplant outcome. Eight hundred ninety-one VUD-HCT donors and their recipients transplanted for a hematologic malignancy in the United Kingdom were retrospectively HLA typed at an ultra-high resolution (UHR) for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 using next-generation sequencing technology. Matching was determined at full gene level for HLA class I and at a coding DNA sequence level for HLA class II genes. The HLA matching status changed in 29.1% of pairs after UHR HLA typing. The 12/12 UHR HLA matched patients had significantly improved 5-year overall survival when compared with those believed to be 12/12 HLA matches based on their original HLA typing but were found to be mismatched after UHR HLA typing (54.8% versus 30.1%, P = .022). Survival was also significantly better in 12/12 UHR HLA-matched patients when compared with those with any degree of mismatch at this level of resolution (55.1% versus 40.1%, P = .005). This study shows that better HLA matching, found when typing is done at UHR that includes exons outside of the ARD, introns, and untranslated regions, can significantly improve outcomes for recipients of a VUD-HCT for a hematologic malignancy and should be prospectively performed at donor selection., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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