Lazaryan, A., T. Wang, S. R. Spellman, H. L. Wang, J. Pidala, T. Nishihori, M. Askar, R. Olsson, M. Oudshoorn, H. Abdel-Azim, A. Yong, M. Gandhi, C. Dandoy, B. Savani, G. Hale, K. Page, M. Bitan, R. Reshef, W. Drobyski, S. G. Marsh, K. Schultz, C. R. Muller, M. A. Fernandez-Vina, M. R. Verneris, M. M. Horowitz, M. Arora, D. J. Weisdorf and S. J. Lee (2016). “Human leukocyte antigen supertype matching after myeloablative hematopoietic cell transplantation with 7/8 matched unrelated donor allografts: A report from the center for international blood and marrow transplant research.” Haematologica: May 2016 [Epub ahead of print].
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The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 vs. 429), -B (230 vs. 92), -C (365 vs. 349), and -DRB1 (153 vs. 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into 6 HLA-A (A01, A01A03, A01A24, A02, A03, A24), 6 HLA-B (B07, B08, B27, B44, B58, B62), 2 HLA-C (C1, C2), and 5 HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II-IV acute graft-versus-host disease (hazard ratio =1.78, p=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II-IV (hazard ratio=3.11, p=0.002) and III-IV (hazard ratio=3.15, p=0.01) acute graft-versus-host- disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II-IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available, and call for future studies to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation.