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 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

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43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)75-87
Number of pages13
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2008

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

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    Yabe, T., Matsuo, K., Hirayasu, K., Kashiwase, K., Kawamura-Ishii, S., Tanaka, H., Ogawa, A., Takanashi, M., Satake, M., Nakajima, K., Tokunaga, K., Inoko, H., Saji, H., Ogawa, S., Juji, T., Sasazuki, T., Kodera, Y., & Morishima, Y. (2008). 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. Biology of Blood and Marrow Transplantation, 14(1), 75-87. https://doi.org/10.1016/j.bbmt.2007.09.012