title: 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.
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.
authors.affiliation: University of Minnesota Medical Center, Fairview, Minneapolis, MN, USA alazarya@umn.edu.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Lazaryan
authors.affiliation: Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.affiliation: Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Wang
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.affiliation: Karolinska University Hospital, Centre for Allogeneic Stem Cell Transplantation, Stockholm, Sweden.
authors.forename: Richard
authors.initials: R
authors.lastname: Olsson
authors.affiliation: Leiden University Medical Centre, The Netherlands.
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.affiliation: Children's Hospital of Los Angeles, CA, USA.
authors.forename: Hisham
authors.initials: H
authors.lastname: Abdel-Azim
authors.affiliation: Royal Adelaide Hospital/SA Pathology, Australia.
authors.forename: Agnes
authors.initials: A
authors.lastname: Yong
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Gandhi
authors.affiliation: Cincinnati Children's Hospital Medical Center, OH, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dandoy
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Bipin
authors.initials: B
authors.lastname: Savani
authors.affiliation: All Children's Hospital, St. Petersburg, FL, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hale
authors.affiliation: Duke University Medical Center, Pediatric Blood and Marrow Transplant, Durham, NC, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Page
authors.affiliation: Tel-Aviv Sourasky Medical Center, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Bitan
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Reshef
authors.affiliation: Froedtert Memorial Lutheran Hospital, Milwaukee, MN, USA.
authors.forename: William
authors.initials: W
authors.lastname: Drobyski
authors.affiliation: Anthony Nolan Research Institute & University College London Cancer Institute, Royal Free Campus, UK.
authors.forename: Steven Ge
authors.initials: SG
authors.lastname: Marsh
authors.affiliation: British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Kirk
authors.initials: K
authors.lastname: Schultz
authors.affiliation: Zentrales Knochenmarkspender-Register Deutschland, Ulm, Germany.
authors.forename: Carlheinz R
authors.initials: CR
authors.lastname: Müller
authors.affiliation: Stanford University Medical Center, CA, USA.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Fernandez-Viña
authors.affiliation: University of Minnesota Medical Center, Fairview, Minneapolis, MN, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.affiliation: Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.affiliation: University of Minnesota Medical Center, Fairview, Minneapolis, MN, USA.
authors.forename: Mukta
authors.initials: M
authors.lastname: Arora
authors.affiliation: University of Minnesota Medical Center, Fairview, Minneapolis, MN, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000628:therapy; D009196:Myeloproliferative Disorders / Q000150:complications / Q000628:therapy; D012189:Retrospective Studies; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; D019653:Myeloablative Agonists