title: Changes in the clinical impact of high-risk human leukocyte antigen allele mismatch combinations on the outcome of unrelated bone marrow transplantation.
abstract: Several high-risk HLA allele mismatch combinations (HR-MMs) for severe acute graft-versus-host disease (GVHD) have been identified by analyzing transplantation outcomes in Japanese unrelated hematopoietic stem cell transplant recipients. In this study, we analyzed the effects of HR-MMs in 3 transplantation time periods. We confirmed that the incidence of grade III to IV acute GVHD in the HR-MM group was significantly higher than that in the low-risk (LR) MM group (hazard ratio [HR], 2.74; P < .0001) in the early time period (1993 to 2001). However, the difference in the incidence of grade III to IV acute GVHD between the HR-MM and LR-MM groups was not statistically significant (HR, 1.06; P = .85 and HR, .40; P = .21, respectively) in the mid (2002 to 2007) and late (2008 to 2011) time periods. Similarly, survival in the HR-MM group was significantly inferior to that in the LR-MM group (HR, 1.46; P = .019) in the early time period, whereas the difference in survival between the 2 groups was not statistically significant in the mid and late time periods (HR, 1.06; P = .75 and HR, .82; P = .58, respectively). In conclusion, the adverse impact of HR-MM has become less significant over time. Unrelated transplantation with a single HR-MM could be a viable option in the absence of a matched unrelated donor or an unrelated donor with a single LR-MM.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. Electronic address: ycanda-tky@umin.ac.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
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 Data Management/Biostatistics, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fuji
authors.affiliation: Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Tastuo
authors.initials: T
authors.lastname: Ichinohe
authors.affiliation: Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan.
authors.forename: Minoko
authors.initials: M
authors.lastname: Takanashi
authors.affiliation: Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Hematology, Meitetsu Hospital, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sao
authors.affiliation: Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology, Hiroshima Red Cross Hospital & Atomic Bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Iwato
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sawada
authors.affiliation: Department of Hematology and Oncology, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Mori
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D012306:Risk; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D006680:HLA Antigens
keywords: Bone marrow transplantation; Graft-versus-host disease; Human leukocyte antigens; Leukemia