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

Aleksandr Lazaryan, Tao Wang, Stephen R. Spellman, Hai Lin Wang, Joseph Pidala, Taiga Nishihori, Medhat Askar, Richard Olsson, Machteld Oudshoorn, Hisham Abdel-Azim, Agnes Yong, Manish Gandhi, Christopher Dandoy, Bipin Savani, Gregory Hale, Kristin Page, Menachem Bitan, Ran Reshef, William Drobyski, Steven Ge MarshKirk Schultz, Carlheinz R. Müller, Marcelo A. Fernandez-Viña, Michael R. Verneris, Mary M. Horowitz, Mukta Arora, Daniel J. Weisdorf, Stephanie J. Lee

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 epitopebinding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 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 six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five 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. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation.

Original languageEnglish (US)
Pages (from-to)1267-1274
Number of pages8
JournalHaematologica
Volume101
Issue number10
DOIs
StatePublished - Sep 30 2016

Bibliographical note

Publisher Copyright:
© 2016 Ferrata Storti Foundation.

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