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    Recipients receiving better HLA-matched hematopoietic cell transplantation grafts, uncovered by a novel HLA typing method, have superior survival: a retrospective study

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    Authors
    Mayor, N
    Hayhurst, J
    Turner, T
    Szydlo, R
    Shaw, B
    Bultitude, W
    Sayno, J
    Tavarozzi, F
    Latham, K
    Anthias, C
    Robinson, J
    Braund, H
    Danby, R
    Perry, J
    Wilson, M
    Bloor, Adrian
    McQuaker, I
    MacKinnon, S
    Marks, D
    Pagliuca, A
    Potter, M
    Potter, V
    Russell, N
    Thomson, K
    Madrigal, J
    Marsh, S
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    Affiliation
    Anthony Nolan Research Institute, Royal Free Hospital, London, United Kingdom
    Issue Date
    2019
    
    Metadata
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    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.
    Citation
    Mayor 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.
    Journal
    Biology of Blood and Marrow Transplantation
    URI
    http://hdl.handle.net/10541/621761
    DOI
    10.1016/j.bbmt.2018.12.768
    PubMed ID
    30935664
    Additional Links
    https://dx.doi.org/10.1016/j.bbmt.2018.12.768
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.bbmt.2018.12.768
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