Early cytomegalovirus reactivation and expansion of CD56brightCD16dim/−DNAM1+ natural killer cells are associated with anti-leukemia effect after haploidentical stem cell transplantation in acute leukemia

Abstract Background Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation, but is suggested to exert a strong anti-leukemia effect owing in part to alterations in the composition of natural killer (NK) cells. We evaluated the impact of early CMV reactivation and changes in NK subset recovery on relapse rate and survival following haploidentical stem cell transplantation (haploSCT) for acute leukemia. Methods Fifty patients with acute leukemia who received haploSCT were analyzed. Expression of T cells and specific receptors (NKG2A, NKG2D, DNAM1, and CD57) on circulating NK cells (CD56 bright CD16 dim/- or CD56 dim CD16 + cells) was serially measured using multiparametric flow cytometry. Results CMV reactivation during the first 100 days was observed in 41 patients (82 %), at a median of 23 days after haploSCT. The incidence of acute graft-versus-host disease (GVHD) and chronic GVHD tended to be higher in patients with CMV reactivation, although this difference was not statistically significant. Multivariate analysis show that CMV reactivation ( P  = 0.011) and a dose of infused T cells > 3.2 × 10 8 /kg ( P  = 0.027) were independent predictors of a reduced relapse risk and only CMV reactivation ( P  = 0.029) was an independent predictor of improved leukemia-free survival (LFS). CD56 bright CD16 dim/− DNAM1 + NK cell counts increased from day 30 to 90 in patients with CMV reactivation, but decreased after day 30 in patients without CMV reactivation. An increase in CD56 bright CD16 dim/− DNAM1 + NK cells was not associated with the occurrence of chronic GVHD, but was associated with a reduced cumulative relapse rate (16.4% vs. 58.0%, P  = 0.019). Multivariate analysis indicates that an increase in the CD56 bright CD16 dim/− DNAM1 + NK cell count was an independent predictor of reduced relapse risk. Conclusions Our study demonstrates a significant correlation between low relapse rates and CMV reactivation as well as the recovery of CD56 bright CD16 dim/− DNAM1 + NK cells, providing valuable information for understanding the plausible immunological mechanism of the graft-versus-leukemia effect.