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 Marsh,
Kirk Schultz,
Carlheinz R. Müller,
Marcelo A. Fernandez-Viña,
Michael R. Verneris,
Mary M. Horowitz,
Mukta Arora,
Daniel J. Weisdorf,
Stephanie J. Lee
Affiliations
Aleksandr Lazaryan
University of Minnesota Medical Center, Fairview, Minneapolis, MN, USA
Tao Wang
Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA
Stephen R. Spellman
Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA
Hai-Lin Wang
Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA
Joseph Pidala
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Taiga Nishihori
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Medhat Askar
Baylor University Medical Center, Dallas, TX, USA
Richard Olsson
Karolinska University Hospital, Centre for Allogeneic Stem Cell Transplantation, Stockholm, Sweden
Machteld Oudshoorn
Leiden University Medical Centre, The Netherlands
Hisham Abdel-Azim
Children’s Hospital of Los Angeles, CA, USA
Agnes Yong
Royal Adelaide Hospital/SA Pathology, Australia
Manish Gandhi
Mayo Clinic, Rochester, MN, USA
Christopher Dandoy
Cincinnati Children’s Hospital Medical Center, OH, USA
Bipin Savani
Vanderbilt University Medical Center, Nashville, TN, USA
Gregory Hale
All Children’s Hospital, St. Petersburg, FL, USA
Kristin Page
Duke University Medical Center, Pediatric Blood and Marrow Transplant, Durham, NC, USA
Menachem Bitan
Tel-Aviv Sourasky Medical Center, Israel
Ran Reshef
Columbia University Medical Center, New York, NY, USA
William Drobyski
Froedtert Memorial Lutheran Hospital, Milwaukee, MN, USA
Steven GE Marsh
Anthony Nolan Research Institute & University College London Cancer Institute, Royal Free Campus, UK
Kirk Schultz
British Columbia’s Children’s Hospital, Vancouver, British Columbia, Canada
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.
