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 journalArticle

    57 Citations (Scopus)

    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

    Fingerprint

    Hematopoietic Stem Cell Transplantation
    Stem cells
    Hazards
    Alleles
    HLA-C Antigens
    Unrelated Donors
    Transplants
    HLA-A Antigens
    HLA-B Antigens
    T-cells
    Mortality
    Cytotoxic T-Lymphocytes
    Graft vs Host Disease
    Hematologic Neoplasms
    Grafts
    Disease-Free Survival
    Research Design
    Antigens

    ASJC Scopus subject areas

    • Hematology
    • Biochemistry
    • Cell Biology
    • Immunology

    Cite this

    Fernandez-Viña, M. A., Wang, T., Lee, S. J., Haagenson, M., Aljurf, M., Askar, M., ... Setterholm, M. (2014). Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation. Blood, 123(8), 1270-1278. https://doi.org/10.1182/blood-2013-10-532671

    Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation. / Fernandez-Viña, Marcelo A.; Wang, Tao; Lee, Stephanie J.; Haagenson, Michael; Aljurf, Mahmoud; Askar, Medhat; Battiwalla, Minoo; Baxter-Lowe, Lee Ann; Gajewski, James; Jakubowski, Ann A.; Marino, Susana; Oudshoorn, Machteld; Marsh, Steven G E; Petersdorf, Effie W.; Schultz, Kirk; Turner, E. Victoria; Waller, Edmund K.; Woolfrey, Ann; Umejiego, John; Spellman, Stephen R.; Setterholm, Michelle.

    In: Blood, Vol. 123, No. 8, 20.02.2014, p. 1270-1278.

    Research output: Contribution to journalArticle

    Fernandez-Viña, MA, Wang, T, Lee, SJ, Haagenson, M, Aljurf, M, Askar, M, Battiwalla, M, Baxter-Lowe, LA, Gajewski, J, Jakubowski, AA, Marino, S, Oudshoorn, M, Marsh, SGE, Petersdorf, EW, Schultz, K, Turner, EV, Waller, EK, Woolfrey, A, Umejiego, J, Spellman, SR & Setterholm, M 2014, 'Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation', Blood, vol. 123, no. 8, pp. 1270-1278. https://doi.org/10.1182/blood-2013-10-532671
    Fernandez-Viña MA, Wang T, Lee SJ, Haagenson M, Aljurf M, Askar M et al. Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation. Blood. 2014 Feb 20;123(8):1270-1278. https://doi.org/10.1182/blood-2013-10-532671
    Fernandez-Viña, Marcelo A. ; Wang, Tao ; Lee, Stephanie J. ; Haagenson, Michael ; Aljurf, Mahmoud ; Askar, Medhat ; Battiwalla, Minoo ; Baxter-Lowe, Lee Ann ; Gajewski, James ; Jakubowski, Ann A. ; Marino, Susana ; Oudshoorn, Machteld ; Marsh, Steven G E ; Petersdorf, Effie W. ; Schultz, Kirk ; Turner, E. Victoria ; Waller, Edmund K. ; Woolfrey, Ann ; Umejiego, John ; Spellman, Stephen R. ; Setterholm, Michelle. / Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation. In: Blood. 2014 ; Vol. 123, No. 8. pp. 1270-1278.
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    AU - Aljurf, Mahmoud

    AU - Askar, Medhat

    AU - Battiwalla, Minoo

    AU - Baxter-Lowe, Lee Ann

    AU - Gajewski, James

    AU - Jakubowski, Ann A.

    AU - Marino, Susana

    AU - Oudshoorn, Machteld

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    AU - Petersdorf, Effie W.

    AU - Schultz, Kirk

    AU - Turner, E. Victoria

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    AU - Woolfrey, Ann

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