Faculty Collaboration Database

Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study. Biol Blood Marrow Transplant 2019 Mar;25(3):443-450

Date

04/03/2019

Pubmed ID

30935664

DOI

10.1016/j.bbmt.2018.12.768

Scopus ID

2-s2.0-85061186899 (requires institutional sign-in at Scopus site)   75 Citations

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.

Author List

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, Marsh SGE

Author

Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Alleles
Female
Hematopoietic Stem Cell Transplantation
Histocompatibility
Histocompatibility Testing
Humans
Male
Middle Aged
Retrospective Studies
Sequence Analysis, DNA
Survival Analysis
Unrelated Donors