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Volume 14, Issue 1, Pages 75-87 (January 2008)


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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

Toshio YabeaCorresponding Author Informationemail address, Keitaro Matsuob, Kouyuki Hirayasuac, Koichi Kashiwasea, Sumiyo Kawamura-Ishiid, Hidenori Tanakaa, Atsuko Ogawaa, Minoko Takanashia, Masahiro Satakea, Kazunori Nakajimaa, Katsushi Tokunagac, Hidetoshi Inokoe, Hiroo Sajif, Seishi Ogawag, Takeo Jujid, Takehiko Sasazukih, Yoshihisa Koderai, Yasuo Morishimaj, Japan Marrow Donor Program

Received 18 July 2007; accepted 21 September 2007.

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.

a Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo, Japan

b Aichi Cancer Center Research Institute, Division of Epidemiology and Prevention, Nagoya, Japan

c University of Tokyo, Department of Human Genetics, Tokyo, Japan

d Japanese Red Cross Central Blood Institute, Tokyo, Japan

e Tokai University School of Medicine, Division of Molecular Science, Isehara, Japan

f HLA Laboratory, NPO, Kyoto, Japan

g Tokyo University Hospital, Tokyo, Japan

h International Medical Center of Japan, Tokyo, Japan

i Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

j Aichi Cancer Center Hospital, Department of Hematology and Cell Therapy, Nagoya, Japan

Corresponding Author InformationCorrespondence and reprint requests: Toshio Yabe, PhD, Japanese Red Cross Tokyo Metropolitan Blood Center, 2-1-67 Tatsumi, Koto-ku, Tokyo 135-8639, Japan; Tel: +81-3-5534-7546; Fax: +81-3-5534-7547.

PII: S1083-8791(07)00489-2

doi:10.1016/j.bbmt.2007.09.012


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