HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation

Ann Woolfrey, John P. Klein, Michael Haagenson, Stephen Spellman, Effie Petersdorf, Machteld Oudshoorn, James Gajewski, Gregory A. Hale, John Horan, Minoo Battiwalla, Susana R. Marino, Michelle Setterholm, Olle Ringden, Carolyn Hurley, Neal Flomenberg, Claudio Anasetti, Marcelo Fernandez-Vina, Stephanie J. Lee

    Research output: Contribution to journalArticle

    140 Scopus citations

    Abstract

    The association between HLA matching and outcome in unrelated-donor peripheral blood stem cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor-recipient pairs who underwent PBSC transplantation between 1999 and 2006 for acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia and received high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were included in the analysis. Outcomes were compared between HLA-matched and HLA-mismatched pairs, adjusting for patient and transplant characteristics. Matching for HLA-A, -B, -C, and -DRB1 alleles (8/8 match) was associated with better survival at 1 year compared with 7/8 HLA-matched pairs (56% vs 47%). Using 8/8 HLA-matched patients as the baseline (n = 1243), HLA-C antigen mismatches (n = 189) were statistically significantly associated with lower leukemia-free survival (relative risk [RR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = .0010), and increased risk for mortality (RR, 1.41; 95% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95% CI, 1.50-2.62; P < .0001). HLA-B antigen or allele mismatching was associated with an increased risk for acute GVHD grade III-IV. No statistically significant differences in outcome were observed for HLA-C allele (n = 61), HLA-A antigen/allele (n = 136), HLA-DRB1 allele (n = 39), or HLA-DQ antigen/allele (n = 114) mismatches compared with 8/8 HLA-matched pairs. HLA mismatch was not associated with relapse or chronic GVHD. HLA-C antigen-mismatched unrelated PBSC donors were associated with worse outcomes compared with 8/8 HLA-matched donors. The study's limited power due to small sample size precludes conclusions about other mismatches.

    Original languageEnglish (US)
    Pages (from-to)885-892
    Number of pages8
    JournalBiology of Blood and Marrow Transplantation
    Volume17
    Issue number6
    DOIs
    StatePublished - Jun 1 2011

    Keywords

    • Disease free survival
    • Graft-vs-Host disease
    • HLA Mismatch
    • HLA-C antigen
    • Hematopoietic cell transplantation

    ASJC Scopus subject areas

    • Hematology
    • Transplantation

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  • Cite this

    Woolfrey, A., Klein, J. P., Haagenson, M., Spellman, S., Petersdorf, E., Oudshoorn, M., Gajewski, J., Hale, G. A., Horan, J., Battiwalla, M., Marino, S. R., Setterholm, M., Ringden, O., Hurley, C., Flomenberg, N., Anasetti, C., Fernandez-Vina, M., & Lee, S. J. (2011). HLA-C Antigen Mismatch Is Associated with Worse Outcome in Unrelated Donor Peripheral Blood Stem Cell Transplantation. Biology of Blood and Marrow Transplantation, 17(6), 885-892. https://doi.org/10.1016/j.bbmt.2010.09.012