title: Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation.
abstract: We examined current outcomes of unrelated donor allogeneic hematopoietic cell transplantation (HCT) to determine the clinical implications of donor-recipient HLA matching. Adult and pediatric patients who had first undergone myeloablative-unrelated bone marrow or peripheral blood HCT for acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome between 1999 and 2011 were included. All had high-resolution typing for HLA-A, -B, -C, and -DRB1. Of the total (n = 8003), cases were 8/8 (n = 5449), 7/8 (n = 2071), or 6/8 (n = 483) matched. HLA mismatch (6-7/8) conferred significantly increased risk for grades II to IV and III to IV acute graft vs host disease (GVHD), chronic GVHD, transplant-related mortality (TRM), and overall mortality compared with HLA-matched cases (8/8). Type (allele/antigen) and locus (HLA-A, -B, -C, and -DRB1) of mismatch were not associated with overall mortality. Among 8/8 matched cases, HLA-DPB1 and -DQB1 mismatch resulted in increased acute GVHD, and HLA-DPB1 mismatch had decreased relapse. Nonpermissive HLA-DPB1 allele mismatch was associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 8/8 (and 10/10) matched cases. Full matching at HLA-A, -B, -C, and -DRB1 is required for optimal unrelated donor HCT survival, and avoidance of nonpermissive HLA-DPB1 mismatches in otherwise HLA-matched pairs is indicated.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Ahn
authors.affiliation: Center for International Blood and Marrow Transplant Research, National Marrow Donor Program, Minneapolis, MN;
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Wang
authors.affiliation: King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia;
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH;
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.affiliation: National Marrow Donor Program, Minneapolis, MN;
authors.forename: Jason
authors.initials: J
authors.lastname: Dehn
authors.affiliation: Stanford Hospital and Clinics, Stanford, CA;
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez Viña
authors.affiliation: University Hospital Basel, Basel, Switzerland;
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.affiliation: Princess Margaret Hospital, Toronto, ON, Canada;
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH;
authors.forename: Rabi
authors.initials: R
authors.lastname: Hanna
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.affiliation: Georgetown University Hospital, Washington, DC;
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Hurley
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN;
authors.forename: Adetola A
authors.initials: AA
authors.lastname: Kassim
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: ZKRD-Zentrales Knochenmarkspender-Register Deutschland, Ulm, Germany;
authors.forename: Carlheinz
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Europdonor Foundation, Leiden University Medical Centre, Leiden, The Netherlands;
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Effie W
authors.initials: EW
authors.lastname: Petersdorf
authors.affiliation: Duke University Medical Center, Durham, NC;
authors.forename: Vinod
authors.initials: V
authors.lastname: Prasad
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, London, United Kingdom; UCL Cancer Institute, University College, London, United Kingdom;
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
authors.affiliation: British Columbia's Children's Hospital, University of British Columbia, Vancouver, BC, Canada;
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Schultz
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, London, United Kingdom; UCL Cancer Institute, University College, London, United Kingdom; Royal Marsden, Sutton, Surrey, United Kingdom;
authors.forename: Bronwen
authors.initials: B
authors.lastname: Shaw
authors.affiliation: University of Calgary, Calgary, AB, Canada; and.
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.affiliation: University of North Carolina Hospitals, Chapel Hill, NC.
authors.forename: William A
authors.initials: WA
authors.lastname: Wood
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality; D059868:HLA-DP beta-Chains / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen