TY - JOUR
T1 - Effects of HLA Allele and Killer Immunoglobulin-Like Receptor Ligand Matching on Clinical Outcome in Leukemia Patients Undergoing Transplantation With T-cell-Replete Marrow From an Unrelated Donor
AU - Morishima, Yasuo
AU - Yabe, Toshio
AU - Matsuo, Keitaro
AU - Kashiwase, Koichi
AU - Inoko, Hidetoshi
AU - Saji, Hiroh
AU - Yamamoto, Ken
AU - Maruya, Etsuko
AU - Akatsuka, Yoshiki
AU - Onizuka, Makoto
AU - Sakamaki, Hisashi
AU - Sao, Hiroshi
AU - Ogawa, Seishi
AU - Kato, Shunichi
AU - Juji, Takeo
AU - Sasazuki, Takehiko
AU - Kodera, Yoshihisa
N1 - Funding Information:
The authors thank the staff members of the transplant center, donor centers, and JMDP office. They also thank Ms. Ryouko Yamauchi for data management. This work was supported in part by a Health and Labor Science Research Grant from the Ministry of Health, Labor and Welfare of Japan (Research on Human Genome, Tissue Engineering); a grant from Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation; Grant-in-Aid B (15390309) from the Japan Society for the Promotion of Science, and a grant (30) from Third-Term Comprehensive Control Research for Cancer from the Ministry of Health, Labor and Welfare, Japan. The institutions participating and registering patients in this study include Hokkaido University Hospital, Sapporo University Hospital, Sapporo Hokuyu Hospital, Japanese Red Cross Asahikawa Hospital, Asahikawa Medical College Hospital, Hirosaki University Hospital, Iwate Medical University Hospital, Tohoku University Hospital, Yamagata University Hospital, Akita University Hospital, Fukushima Medical College, Toranomon Hospital, National Cancer Center Central Hospital, National Center for Child Health and Development, Institute of Medical Science at the University of Tokyo, Toho University Hospital, Omori Hospital, Tokyo Metropolitan Komagome Hospital, Nihon University Hospital, Itabashi Hospital, Jikei University Hospital, Keio University Hospital, Tokyo Medical College Hospital, Tokyo Medical and Dental University Hospital, Tokyo University Hospital, Yokohama City University Hospital, Kanagawa Children’s Medical Center, Kanagawa Cancer Center, Tokai University Hospital, St. Marianna University Hospital, Chiba University Hospital, Chiba Children’s Hospital, Kameda General Hospital, Saitama Children’s Medical Center, Saitama Cancer Center Hospital, Saitama Medical School Hospital, Ibaraki Children’s Hospital, Jichi Medical School Hospital, Tsukuba University Hospital, Dokkyo University Hospital, Saiseikai Maebashi Hospital, Gunma University Hospital, Niigata University Hospital, Niigata Cancer Center Hospital, Shinshu University Hospital, Hamamatsu University Hospital, Hamamatsu Medical Center, Shizuoka General Hospital, Shizuoka Children’s Hospital, Japanese Red Cross Nagoya First Hospital, Nagoya Daini Red Cross Hospital, Meitetsu Hospital, Nagoya University Hospital, Nagoya Ekisaikai Hospital, Nagoya Medical Center, Aichi Cancer Center Hospital, Aichi Medical University Hospital, Nagoya City University Hospital, Showa Hospital, Anjo Kousei Hospital, Fujita Health University Hospital, Mie University Hospital, Yamada Red Cross Hospital, Kanazawa University Hospital, Kanazawa Medical University Hospital, Toyama Prefectural Central Hospital, Fukui Medical School Hospital, Shiga University of Medical Science, Center for Adult Disease in Osaka, Kinki University Hospital, Osaka University Hospital, Osaka City University Hospital, Osaka Medical Center and Research Institute for Maternal and Child Health, Matsushita Memorial Hospital, Hyogo College of Medicine Hospital, Hyogo Medical Center for Adults, Kobe City General Hospital, Kobe University Hospital, Kyoto University Hospital, Kyoto Prefectural University of Medicine Hospital, Kyoto City Hospital, Kansai Medical University Hospital, Tenri Hospital, Nara Medical University Hospital, Tottori University Hospital, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Yamaguchi University Hospital, Ehime Prefectural Central Hospital, Okayama Medical Center, Kurashiki Central Hospital, Kyushu University Hospital, Harasanshin General Hospital, Hamanomachi General Hospital, National Kyushu Cancer Center, St. Mary’s Hospital, Kokura Memorial Hospital, Nagasaki University Hospital, Kumamoto Medical Center, Oita Medical University Hospital, Imamura Hospital, and Kagoshima University Hospital.
PY - 2007/3
Y1 - 2007/3
N2 - The responsible human leukocyte antigen (HLA) locus and the role of killer immunoglobulin-like receptor (KIR) ligand matching on transplantation outcome were simultaneously identified by multivariate analysis in 1790 patients with leukemia who underwent transplantation with T-cell-replete marrow from an unrelated donor (UR-BMT) through the Japan Marrow Donor Program. The graft-versus-leukemia (GVL) effect depended on leukemia cell type. HLA-C mismatch reduced the relapse rate in acute lymphoblastic leukemia (ALL) (hazard ratio [HR] = 0.47; P = .003), and HLA-DPB1 mismatch reduced it in chronic myeloid leukemia (CML) (HR = 0.35; P < .001). In contrast, KIR2DL ligand mismatch in the graft-versus-host (GVH) direction (KIR-L-MM-G) increased in ALL (HR = 2.55; P = .017). An increased rejection rate was observed in KIR2DL ligand mismatch in the host-versus-graft direction (HR = 4.39; P = .012). Acute GVH disease (GVHD) was increased not only in the mismatch of HLA-A, -B, -C, and -DPB1, but also in KIR-L-MM-G. As a whole, the mismatch of HLA-A, -B, and -DQB1 locus and KIR-L-MM-G resulted in increased mortality. In conclusion, not only the mismatch of HLA-C and -DPB1, but also KIR-L-MM-G affected leukemia relapse, which should be considered based on leukemia cell type. Furthermore, KIR-L-MM induced adverse effects on acute GVHD (aGVHD) and rejection, and brought no survival benefits to patients with T-cell-replete UR-BMT.
AB - The responsible human leukocyte antigen (HLA) locus and the role of killer immunoglobulin-like receptor (KIR) ligand matching on transplantation outcome were simultaneously identified by multivariate analysis in 1790 patients with leukemia who underwent transplantation with T-cell-replete marrow from an unrelated donor (UR-BMT) through the Japan Marrow Donor Program. The graft-versus-leukemia (GVL) effect depended on leukemia cell type. HLA-C mismatch reduced the relapse rate in acute lymphoblastic leukemia (ALL) (hazard ratio [HR] = 0.47; P = .003), and HLA-DPB1 mismatch reduced it in chronic myeloid leukemia (CML) (HR = 0.35; P < .001). In contrast, KIR2DL ligand mismatch in the graft-versus-host (GVH) direction (KIR-L-MM-G) increased in ALL (HR = 2.55; P = .017). An increased rejection rate was observed in KIR2DL ligand mismatch in the host-versus-graft direction (HR = 4.39; P = .012). Acute GVH disease (GVHD) was increased not only in the mismatch of HLA-A, -B, -C, and -DPB1, but also in KIR-L-MM-G. As a whole, the mismatch of HLA-A, -B, and -DQB1 locus and KIR-L-MM-G resulted in increased mortality. In conclusion, not only the mismatch of HLA-C and -DPB1, but also KIR-L-MM-G affected leukemia relapse, which should be considered based on leukemia cell type. Furthermore, KIR-L-MM induced adverse effects on acute GVHD (aGVHD) and rejection, and brought no survival benefits to patients with T-cell-replete UR-BMT.
UR - https://www.scopus.com/pages/publications/33847072633
UR - https://www.scopus.com/pages/publications/33847072633#tab=citedBy
U2 - 10.1016/j.bbmt.2006.10.027
DO - 10.1016/j.bbmt.2006.10.027
M3 - Article
C2 - 17317585
AN - SCOPUS:33847072633
SN - 1083-8791
VL - 13
SP - 315
EP - 328
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -
