title: Impact of Human Leukocyte Antigen Allele Mismatch in Unrelated Bone Marrow Transplantation with Reduced-Intensity Conditioning Regimen.
abstract: The impact of HLA mismatch in hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) has not been fully examined. We analyzed a total of 1130 cases to examine the effects of HLA allele mismatch in unrelated bone marrow transplantation (BMT) with RIC in the Japan Marrow Donor Program registry cohort. Compared with HLA 8/8-allele match (n = 720, 8/8 match), both 1 (n = 295, 7/8 match) and 2 allele mismatches (n = 115, 6/8 match) were associated with significant reduction of overall survival (OS) (hazard ratio [HR],  1.34; P = .0024 and HR, 1.33; P = .035 for 7/8 and 6/8 match, respectively). The incidence of grades 2 to 4 acute graft-versus-host disease (aGVHD) increased with increasing number of mismatched alleles (HR, 1.36 and HR, 2.08 for 7/8 and 6/8 match, respectively). Nonrelapse mortality showed a similar tendency to aGVHD (HR, 1.35 for 7/8 and HR, 1.63 for 6/8). One-allele mismatches at the HLA-A or -B and HLA-C loci were significantly associated with inferior OS compared with 8/8 match (HR, 1.64 for A or B mismatch and HR, 1.41 for C mismatch), whereas HLA-DRB1 allele mismatch was not (HR, 1.16; P = .30). However, the effect of HLA-A or -B and -C mismatch on OS was not observed in those who received RIC BMT since 2010, in contrast to recipients before 2010. These results suggested that in unrelated RIC BMT, 1-allele mismatch is associated with poorer outcome, and the impact of HLA mismatch may differ depending on the HLA locus, although these HLA mismatch effects may be different in recent cases.
authors.affiliation: Department of Hematology, Sendai Medical Center, National Hospital Organization, Sendai, Japan. Electronic address: yokoyamah@snh.go.jp.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fuji
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
authors.forename: Yuho
authors.initials: Y
authors.lastname: Najima
authors.affiliation: Departments of Hematology, Tenri Hospital, Tenri, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Uchida
authors.affiliation: Department of Haematology/Oncology and Transfusion and Haemapheresis Center, Kurashiki Central Hospital, Kurashiki, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.affiliation: Department of Hematology, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Iwato
authors.affiliation: Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Hematology/Oncology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe
authors.affiliation: Japanese Data Center for Hematopoietic Cell Transplantation, Japan; Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D019520:Living Donors; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009504:Neutrophils; D012189:Retrospective Studies; D012306:Risk; D019172:Transplantation Conditioning / Q000379:methods*; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D002066:Busulfan; D008558:Melphalan
keywords: HLA mismatch; Reduced-intensity conditioning; Unrelated bone marrow transplantation