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HLA-B Leader and Survivorship after HLA-Mismatched Unrelated Donor Transplantation

  1. Author:
    Petersdorf, Effie W
    Stevenson, Philip
    Bengtsson, Mats
    De Santis, Dianne
    Dubois, Valerie
    Gooley, Ted
    Horowitz, Mary M
    Hsu, Katharine C
    Madrigal, Alejandro J
    Malkki, Mari
    McKallor, Caroline
    Morishima, Yasuo
    Oudshoorn, Machteld
    Spellman, Stephen
    Villard, Jean
    Carrington,Mary

  2. Author Address

    University of Washington, United States., Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., University of Uppsala, Uppsala, Sweden., PathWest, Fiona Stanley Hospital, Perth, Australia., EFS AURA, LYON, France., Fred Hutchinson, Seattle, Washington, United States., Medical College of Wisconsin, United States., Memorial Sloan-Kettering Cancer Center, New York, New York, United States., Anthony Nolan Trust., Aichi Medical University, Nagoya, Japan., Leiden University Medical Center, Leiden, Leiden, Netherlands., Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota, United States., Immunology and Transplant Unit, Geneva, Switzerland., Frederick National Laboratory, Frederick, Maryland, United States.,
    1. Year: 2020
    2. Date: JUL 16
    3. Epub Date: 2020 06 01
  2. Journal: Blood
    1. 136
    2. 3
    3. Pages: 362-369
  4. Type of Article: Article
  5. ISSN: 0006-4971
  1. Abstract:

    Hematopoietic-cell transplantation (HCT) from HLA-mismatched unrelated donors can cure life-threatening blood disorders but its success is limited by graft-versus-host disease (GVHD). HLA-B leaders encode methionine (M) or threonine (T) at position 2 and give rise to TT, MT or MM genotypes. The dimorphic HLA-B leader informs GVHD risk in HLA-B-mismatched HCT. If the leader influences outcome in other HLA-mismatched transplant settings, the success of HCT could be improved for future patients. We determined leader genotypes for 11872 patients transplanted between 1988 and 2016 from unrelated donors with one HLA-A -B,-C,-DRB1 or -DQB1 mismatch. Multivariate regression methods were used to evaluate risks associated with patient leader genotype according to the mismatched HLA locus and with HLA-A,-B,-C,-DRB1 or -DQB1 mismatching according to patient leader genotype. The impact of the patient leader genotype on acute GVHD and mortality varied across different mismatched HLA loci. Non-relapse mortality was higher among HLA-DQB1-mismatched MM patients compared to HLA-DQB1-mismatched TT patients (hazard ratio 1.35; P = .01). Grades III-IV GVHD risk was higher among HLA-DRB1-mismatched MM or MT patients compared to HLA-DRB1-mismatched TT patients (odds ratio 2.52 and 1.51, respectively). Patients tolerated a single HLA-DQB1 mismatch better than mismatches at other loci. Outcome after HLA-mismatched transplantation depends on the HLA-B leader dimorphism and the mismatched HLA locus. The patient's leader variant provides new information on the limits of HLA mismatching. The success of HLA-mismatched unrelated transplantation might be enhanced through the judicious selection of mismatched donors for a patient's given leader genotype. Copyright © 2020 American Society of Hematology.

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External Sources

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  2. DOI: 10.1182/blood.2020005743
  3. PMID: 32483623
  4. View record in Web of Science®
  5. WOS: 000550485600014
  6. PII : 460604

Library Notes

  1. Fiscal Year: FY2019-2020
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