title: Influence of Differently Licensed KIR2DL1-Positive Natural Killer Cells in Transplant Recipients with Acute Leukemia: A Japanese National Registry Study.
abstract: Licensing by self MHC class I ligands is required for proper natural killer (NK) cell response. NK cells with inhibitory killer cell immunoglobulin-like receptors for nonself MHC exhibit transient alloreactivity after hematopoietic stem cell transplantation (HSCT). We analyzed 3866 recipients in the Japan national registry who underwent their first allogeneic HSCT for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) from HLA-A, -B, and -DRB1 allele-genomatched unrelated donors. By classifying them into 5 independent groups based on HLA-C group matching and assumed donor NK cell status, we found that for HLA-C-matched HSCT for AML in HLA-C1/C1 recipients, in whom transient alloreactivity against HLA-C2-negative leukemic cells was expected, the relapse rate was significantly lower than it was in HLA-C-matched HSCT for AML in HLA-C1/C2 recipients (hazard ratio [HR], .72; P = .011). This difference was not observed in HLA-C-matched HSCT for ALL. Compared with HLA-C-matched HSCT, significantly higher mortality was observed in HLA-C1/C1 AML patients who received transplants from HLA-C-mismatched HLA-C1/C1 donors (HR, 1.37; P = .001) and in HLA-C1/C1 ALL patients who received transplants from HLA-C2-positive donors (HR, 2.13; P = .005). In conclusion, donor selection based on leukemic subtype and donor HLA-C group matching improves transplantation outcome after HLA-C-mismatched HSCT.
authors.affiliation: Department of Hematology, Medical Research Institute Kitano Hospital, Osaka, Japan. Electronic address: n-arima@kitano-hp.or.jp.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Arima
authors.affiliation: Department of Public Health/Health Policy, The University of Tokyo, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: Hematology Division, Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Yabe
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fuji
authors.affiliation: Hematology Division, Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Division of Hematopoietic Stem Cell Transplantation, 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: 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, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.affiliation: Department of Hematology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Hoshino
authors.affiliation: Department of Hematology, Meitetsu hospital, Nagoya, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kato
authors.affiliation: Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Heiwa
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Department of Hematology, Osaka City University Hospital, Osaka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.affiliation: Japanese Data Center for Hematopoietic Cell Transplantation/Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Department of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D054342:Receptors, KIR2DL1 / Q000235:genetics / Q000276:immunology; D012042:Registries; D015996:Survival Rate
chemical_list: D015236:HLA-C Antigens; C093100:KIR2DL1 protein, human; D054342:Receptors, KIR2DL1
keywords: Acute leukemia; Allogeneic hematopoietic stem cell transplantation; HLA-C mismatch; Killer cell immunoglobulin-like receptor; Natural killer cell