Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study

Neema P. Mayor, James D. Hayhurst, Thomas R. Turner, Richard M. Szydlo, Bronwen E. Shaw, Will P. Bultitude, Jex Ray Sayno, Franco Tavarozzi, Katy Latham, Chloe Anthias, James Robinson, Henny Braund, Robert Danby, Julia Perry, Marie C. Wilson, Adrian J. Bloor, I. Grant McQuaker, Stephen MacKinnon, David I. Marks, Antonio PagliucaMichael N. Potter, Victoria T. Potter, Nigel H. Russell, Kirsty J. Thomson, J. Alejandro Madrigal, Steven G.E. Marsh*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

47 Citations (Scopus)
187 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)443-450
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number3
DOIs
Publication statusPublished - 29 Mar 2019

Keywords

  • HLA matching
  • Next-generation sequencing
  • Survival
  • Ultra-high resolution HLA typing
  • Unrelated donor hematopoietic cell transplantation

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