Recipients receiving better HLA-matched hematopoietic cell transplantation grafts, uncovered by a novel HLA typing method, have superior survival: a retrospective study
AffiliationAnthony Nolan Research Institute, Royal Free Hospital, London, United Kingdom
MetadataShow full item record
AbstractHLA 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.
CitationMayor NP, Hayhurst JD, Turner TR, Szydlo RM, Shaw BE, Bultitude WP, et al. 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):443-50.
JournalBiology of Blood and Marrow Transplantation
- Direct HLA Genetic Comparisons Identify Highly Matched Unrelated Donor-Recipient Pairs with Improved Transplantation Outcome.
- Authors: Vazirabad I, Chhabra S, Nytes J, Mehra V, Narra RK, Szabo A, Jerkins JH, Dhakal B, Hari P, Anderson MW
- Issue date: 2019 May
- High resolution HLA class I and II typing and CTLp frequency in unrelated donor transplantation: a single-institution retrospective study of 69 BMTs.
- Authors: El Kassar N, Legouvello S, Joseph CM, Salesses P, Rieux C, Cordonnier C, Vernant JP, Farcet JP, Bierling P, Kuentz M
- Issue date: 2001 Jan
- Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study.
- Authors: Fleischhauer K, Shaw BE, Gooley T, Malkki M, Bardy P, Bignon JD, Dubois V, Horowitz MM, Madrigal JA, Morishima Y, Oudshoorn M, Ringden O, Spellman S, Velardi A, Zino E, Petersdorf EW, International Histocompatibility Working Group in Hematopoietic Cell Transplantation.
- Issue date: 2012 Apr
- High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis.
- Authors: Fürst D, Müller C, Vucinic V, Bunjes D, Herr W, Gramatzki M, Schwerdtfeger R, Arnold R, Einsele H, Wulf G, Pfreundschuh M, Glass B, Schrezenmeier H, Schwarz K, Mytilineos J
- Issue date: 2013 Oct 31
- Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival.
- Authors: Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C, Setterholm M, Drexler R, Maiers M, King R, Confer D, Klein J
- Issue date: 2008 Jul