title: Donor killer immunoglobulin-like receptor (KIR) genotype-patient cognate KIR ligand combination and antithymocyte globulin preadministration are critical factors in outcome of HLA-C-KIR ligand-mismatched T cell-replete unrelated bone marrow transplantation.
abstract: We previously reported the potent adverse effects of killer immunoglobulin-like receptor (KIR) ligand mismatch (KIR-L-MM) on the outcome of T cell-replete unrelated hematopoietic stem cell transplantation (UR-HSCT) through the Japan Marrow Donor Program. Other UR-HSCT studies have yielded inconsistent results. To address this discrepancy, we evaluated candidate factors contributing to the effects of KIR-L-MM on transplantation outcomes in retrospectively selected hematologic malignancy cases with uniform graft-versus-host disease (GVHD) prophylaxis (n = 1489). KIR-L-MM in the graft-versus-host direction (KIR-L-MM-G) was associated with a higher incidence of acute GVHD (aGVHD; P < .002) and a lower overall survival (OS; P < .0001) only without the preadministration of antithymocyte globulin (ATG). Furthermore, in KIR-L-MM-G, the donor KIR2DS2 gene with the patient cognate C1 ligand was associated with a higher incidence of aGVHD (P = .012). Multivariate analysis by Cox proportional hazard models suggested that donor 2DS2 and ATG preadministration were critical factors in grade III-IV aGVHD (hazard ratio = 1.96; 95% confidence interval = 1.01-3.80; P = .045, and hazard ratio = 0.56; 95% confidence interval = 0.31-0.99; P = .047, respectively). These results indicate that the adverse effects of KIR-L-MM-G depend on combination of donor-activating KIR genotype-patient cognate KIR ligand type and no ATG preadministration, thereby suggesting the importance of these factors in UR-HSCT and in leukemia treatment using natural killer (NK) cell alloreactivity.
authors.affiliation: Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo, Japan. to-yabe@tokyo.bc.jrc.or.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Yabe
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kouyuki
authors.initials: K
authors.lastname: Hirayasu
authors.forename: Koichi
authors.initials: K
authors.lastname: Kashiwase
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Kawamura-Ishii
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ogawa
authors.forename: Minoko
authors.initials: M
authors.lastname: Takanashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Satake
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Hiroo
authors.initials: H
authors.lastname: Saji
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Takeo
authors.initials: T
authors.lastname: Juji
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006086:Graft vs Host Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000628:therapy; D008024:Ligands; D008297:Male; D054340:Receptors, KIR / Q000235:genetics*; D054344:Receptors, KIR2DL3 / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D000961:Antilymphocyte Serum; C515078:KIR2DL3 protein, human; D008024:Ligands; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3