• Toshio Yabe, Keitaro Matsuo, Kouyuki Hirayasu, Koichi Kashiwase, Sumiyo Kawamura-Ishii, Hidenori Tanaka, Atsuko Ogawa, Minoko Takanashi, Masahiro Satake, Kazunori Nakajima, Katsushi Tokunaga, Hidetoshi Inoko, Hiroo Saji, Seishi Ogawa, Takeo Juji, Takehiko Sasazuki, Yoshihisa Kodera, Yasuo Morishima, and Japan Marrow Donor Program.
• Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo, Japan. to-yabe@tokyo.bc.jrc.or.jp
• Biol. Blood Marrow Transplant. 2008 Jan 1; 14 (1): 75-87.

AbstractWe 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.

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