Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation

Marcelo A. Fernandez-Viña, Tao Wang, Stephanie J. Lee, Michael Haagenson, Mahmoud Aljurf, Medhat Askar, Minoo Battiwalla, Lee Ann Baxter-Lowe, James Gajewski, Ann A. Jakubowski, Susana Marino, Machteld Oudshoorn, Steven G.E. Marsh, Effie W. Petersdorf, Kirk Schultz, E. Victoria Turner, Edmund K. Waller, Ann Woolfrey, John Umejiego, Stephen R. SpellmanMichelle Setterholm

    Research output: Contribution to journalArticlepeer-review

    60 Scopus citations

    Abstract

    In subjects mismatched in the HLA alleles C*03:03/C*03:04 no allogeneic cytotoxic T-lymphocyte responses are detected in vitro. Hematopoietic stem cell transplantation (HSCT) with unrelated donors (UDs) showed no association between the HLA-C allele mismatches (CAMMs) and adverse outcomes; antigen mismatches at this and mismatches other HLA loci are deleterious. The absence of effect of the CAMM may have resulted from the predominance of the mismatch C*03:03/C*03:04. Patients with hematologic malignancies receiving UD HSCT matched in 8/8 and 7/8 HLA alleles were examined. Transplants mismatched in HLA-C antigens or mismatched in HLA-A, -B, or -DRB1 presented significant differences (P < .0001) in mortality (hazard ratio [HR] 5 1.37, 1.30), disease-free survival (HR 5 1.33, 1.27), treatment-related mortality (HR 5 1.54, 1.54), and grade 3-4 acute graft-versus-host disease (HR 5 1.49, 1.77) compared with the 8/8 group; transplants mismatched in other CAMMs had similar outcomes with HR ranging from 1.34 to 172 for these endpoints. The C*03:03/C*03:04 mismatched and the 8/8 matched groups had identical outcomes (HR ranging from 0.96-1.05). The previous finding that CAMMs do not associate with adverse outcomes is explained by the predominance (69%) of the mismatch C*03:03/03:04 in this group that is better tolerated than other HLA mismatches.

    Original languageEnglish (US)
    Pages (from-to)1270-1278
    Number of pages9
    JournalBlood
    Volume123
    Issue number8
    DOIs
    StatePublished - Feb 20 2014

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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