| Literature DB >> 27247320 |
Aleksandr Lazaryan1, Tao Wang2, Stephen R Spellman3, Hai-Lin Wang2, Joseph Pidala4, Taiga Nishihori4, Medhat Askar5, Richard Olsson6, Machteld Oudshoorn7, Hisham Abdel-Azim8, Agnes Yong9, Manish Gandhi10, Christopher Dandoy11, Bipin Savani12, Gregory Hale13, Kristin Page14, Menachem Bitan15, Ran Reshef16, William Drobyski17, Steven Ge Marsh18, Kirk Schultz19, Carlheinz R Müller20, Marcelo A Fernandez-Viña21, Michael R Verneris22, Mary M Horowitz2, Mukta Arora22, Daniel J Weisdorf22, Stephanie J Lee23.
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 epitope-binding 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. Copyright© Ferrata Storti Foundation.Entities:
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Year: 2016 PMID： 27247320 PMCID： PMC5046657 DOI： 10.3324/haematol.2016.143271
Source DB: PubMed Journal: Haematologica ISSN： 0390-6078 Impact factor: 9.941