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.
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.
Yabe
Toshio
T
Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo, Japan. to-yabe@tokyo.bc.jrc.or.jp
Matsuo
Keitaro
K
Hirayasu
Kouyuki
K
Kashiwase
Koichi
K
Kawamura-Ishii
Sumiyo
S
Tanaka
Hidenori
H
Ogawa
Atsuko
A
Takanashi
Minoko
M
Satake
Masahiro
M
Nakajima
Kazunori
K
Tokunaga
Katsushi
K
Inoko
Hidetoshi
H
Saji
Hiroo
H
Ogawa
Seishi
S
Juji
Takeo
T
Sasazuki
Takehiko
T
Kodera
Yoshihisa
Y
Morishima
Yasuo
Y
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
D000961:Antilymphocyte Serum; C515078:KIR2DL3 protein, human; D008024:Ligands; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3