The impact of the dose of natural killer cells in the graft on severe acute graft-versus-host disease after unrelated bone marrow transplantation

Abstract

The impact of lymphocyte subpopulations on the outcome of bone marrow transplantation (BMT) remains uncertain. We investigated the relationship between the lymphocyte subpopulations of bone marrow grafts and the outcome of BMT. A total of 121 patients who underwent BMT at Kanagawa Cancer Center between 2000 and 2009 were analyzed. Grade III–IV acute graft-versus-host disease (GVHD) occurred in 35.9% of patients who received unrelated BMT with a CD56 cell dose ≤2.80×106/kg versus only 9.7% of patients with a CD56 cell dose >2.80×106/kg (P=0.017). In patients receiving related BMT, the cumulative incidence of grade III–IV acute GVHD did not differ significantly in relation to the CD56 cell dose. On multivariate analysis, older donor age (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03–1.15, P=0.004) and a high dose of CD56 cells (>2.80×106/kg) (HR: 0.15, 95%CI: 0.03–0.92, P=0.040) were significant determinants of grade III–IV acute GVHD after unrelated BMT. None of the lymphocyte subpopulations had a significant impact on the outcome of transplantation, including the rate of neutrophil engraftment, relapse, relapse-free mortality, and overall survival. Our findings suggest that a high natural killer cell dose prevents severe acute GVHD after unrelated BMT, while sparing the graft-versus-leukemia effect.