Faculty Collaboration Database

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 2016 Oct;101(10):1267-1274

Date

06/02/2016

Pubmed ID

27247320

Pubmed Central ID

PMC5046657

DOI

10.3324/haematol.2016.143271

Scopus ID

2-s2.0-84989295930 (requires institutional sign-in at Scopus site)   16 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 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.

Author List

Lazaryan A, Wang T, Spellman SR, Wang HL, Pidala J, Nishihori T, Askar M, Olsson R, Oudshoorn M, Abdel-Azim H, Yong A, Gandhi M, Dandoy C, Savani B, Hale G, Page K, Bitan M, Reshef R, Drobyski W, Marsh SG, Schultz K, Müller CR, Fernandez-Viña MA, Verneris MR, Horowitz MM, Arora M, Weisdorf DJ, Lee SJ

Authors

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Kristin Page MD, MHS, MEd Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Allografts
Child
Child, Preschool
Female
Graft vs Host Disease
HLA Antigens
HLA-B Antigens
Hematopoietic Stem Cell Transplantation
Histocompatibility
Humans
Infant
Leukemia
Male
Middle Aged
Myeloablative Agonists
Myelodysplastic Syndromes
Myeloproliferative Disorders
Retrospective Studies
Unrelated Donors
Young Adult