CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors

Killer immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction was demonstrated to be associated with improved outcome in pa-tients given haploidentical, T-cell– depleted hematopoietic stem cell trans-plants (HSCTs). The goal of this study was to evaluate whether that observation could be generalized for patients receiv-ing unmanipulated HSCTs from unrelated donors (URD). One hundred thirty pa-tients with hematologic malignancies en-tered the study. Graft-versus-host dis-ease (GVHD) prophylaxis was uniform and consisted of cyclosporin, short-term methotrexate, and pretransplantation an-tithymocyte globulin (ATG). Patients were divided into those with (n 20) and those without (n 110) KIR ligand incompatibil-ity with respect to their donors. At 4.5 years patients with KIR ligand incompat-ibility had higher probability of overall survival (87 % versus 48%, P .006) and disease-free survival (87 % versus 39%, P .0007) compared with those without KIR ligand incompatibility. Transplant-related mortality for the 2 groups equaled 6 % and 40 % (P .01), respectively. Re-lapse rates for patients receiving trans-plants from a donor with or without KIR ligand incompatibility were 6 % and 21%, respectively (P .07). All patients with myeloid malignancies receiving trans-plants from KIR ligand–disparate donors (n 13) are alive and disease free. These data indicate that natural killer (NK) cell alloreactivity is associated with better outcome after URD-HSC transplantation when ATG is used as part of GVHD pro-phylaxis. (Blood. 2003;102:814-819) © 2003 by The American Society of Hematolog