Effects of the NK Cell Recovery on Outcomes of Unmanipulated Haploidentical Blood and Marrow Transplantation for Patients with Hematologic Malignancies

The goal of this study was to investigate the association of natural killer (NK) cell recovery with clinical outcomes after unmanipulated haploidentical blood and marrow transplantation. We sequentially monitored the reconstitution kinetics of circulating NK cells, CD56(bright) and CD56(dim), in 43 patients by flow cytometry, and the functionality recovery of cytokine or cytotoxicity of NK cells by flow cytometry or lactate dehydrogenase release assay after transplantation. Reconstitution of NK cells was rapid but accompanied by skewing of cell subsets mainly in CD56(bright), which recovered earlier. Linear regression analysis demonstrated that dose of CD34(+) cells in the allografts was inversely correlated with the ratio of T/NK cells (beta = -0.506, P = .003) and CD56(dim)/CD56(bright) cell (beta = -.403, P = .018) by day 14 after hematopoietic stem cell transplantation (HSCT), and the dose of CD3(+) T cells in the allografts was also inversely correlated with the ratio CD56(dim)/CD56(bright) cells by day 14 after HSCT (beta = -0.474, P = .005). Moreover, the dose of CD56(dim) NK cells in the allograft was positively associated with the day 14 CD56(brigh) NK cells (beta = 0.494, P = .032) and inversely correlated with the day 14 ratio of CD56(dim)/CD56(bright) cells (beta = -0.617, P = .005). Compared with nonacute graft-versus-host disease (GVHD) patients, patients with acute GVHD (aGVHD) had a higher level of NK subsets during week 2 posttransplantation. Cox regression analysis revealed that the patients with more CD56(bright) NK cells in the recovery stage had a higher survival rate (hazard risk HR, 0.406; P = .017) and the patients with a higher ratio of T/NK (>1.0) had a higher chance of getting aGVHD (HR, 3.436; P = .059) and chronic GVHD (HR, 3.925; P = .028). Our results suggest that the recovery of NK cells is and can be used as an indicator to predicate the clinical outcomes after unmanipulated haploidentical transplantation.