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

Effects of KIR ligand mismatch on transplantation outcome. Cumulative incidence of acute GVHD (grade III-IV) (A) and overall survival (B) by matching of KIR ligands in the GVHD direction. The directions of HLA-C mismatching were GVH and/or HVG. All patients were analyzed. The solid line represents HLA-C match (CM), the thin dotted line represents HLA-C mismatch KIR ligand match in the GVHD direction (C-MM KIR-L-M), and the thick dotted line represents HLA-C mismatch KIR ligand mismatch in the GVH direction (C-MM KIR-L-MM-G). The log-rank test was applied between CMM KIR-L-MM-G and CMM KIR-L-M.

Effects of donor KIR2DS2 in KIR ligand mismatch on transplantation outcome: Cumulative incidence of aGVHD, relapse, and overall survival with presence or absence of donor KIR2DS2 gene in HLA-C–mismatched patients. Grade III-IV GVHD (A and E), grade 2-4 GVHD (B and F), relapse (C and G), and overall survival (D and H) with KIR-L-MM-G (A-D) or KIR-L-M (E-H) cases were analyzed. The solid line represents donor KIR2DS2-positive; the dotted line, donor KIR2DS2-negative.

Effects of ATG preadministration in KIR ligand mismatch on transplantation outcome: Cumulative incidence of aGVHD, relapse, and overall survival of patients not receiving ATG (A-C) and those receiving ATG (D-F). The solid line represents HLA-C match (C-M), the thick dotted line represents HLA-C mismatch KIR ligand match in the GVHD direction (C-MM KIR-L-M), and the thin dotted line represents HLA-C mismatch KIR ligand mismatch in the GVH direction (C-MM KIR-L-MM-G). The log-rank test was applied between CMM KIR-L-MM-G and CMM KIR-L-M.

Model of interaction between activating KIR and cognate KIR ligand. Donor-activating KIR transduces an activating signal on recognition of the cognate KIR ligand of the patient cell in KIR-L-MM-G case (B). The activating signal is canceled by an inhibitory signal from inhibitory KIR, which recognizes the KIR ligand of the patient cell in KIR-L-M case (D).