title: Biological significance of HLA locus matching in unrelated donor bone marrow transplantation.
abstract: We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan;
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan;
authors.forename: Koichi
authors.initials: K
authors.lastname: Kashiwase
authors.affiliation: Department of Preventive Medicine, Kyushu University School of Medicine, Fukuoka, Japan;
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan;
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Azuma
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan;
authors.forename: Satoko
authors.initials: S
authors.lastname: Morishima
authors.affiliation: Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan;
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.affiliation: Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan;
authors.forename: Toshio
authors.initials: T
authors.lastname: Yabe
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
authors.affiliation: Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan;
authors.forename: Noriko
authors.initials: N
authors.lastname: Doki
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan;
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.affiliation: Division of Hematology, Keio University School of Medicine, Tokyo, Japan;
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan;
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.affiliation: Department of Hematology, Meitetsu Hospital, Nagoya, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sao
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: HLA Laboratory, Kyoto, Japan;
authors.forename: Hiroo
authors.initials: H
authors.lastname: Saji
authors.affiliation: Department of Cell Transplantation, Tokai University School of Medicine, Isehara, Japan;
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kato
authors.affiliation: Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Japanese Red Cross Kinki Block Blood Center, Osaka, Japan;
authors.forename: Keisei
authors.initials: K
authors.lastname: Kawa
authors.affiliation: Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University, Aichi, Japan; and.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
authors.affiliation: Institute for Advanced Study, Kyushu University, Fukuoka, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data; D002648:Child; D002675:Child, Preschool; D005260:Female; D056426:Genetic Loci / Q000276:immunology; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D059868:HLA-DP beta-Chains / Q000235:genetics / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006648:Histocompatibility / Q000502:physiology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains