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, CD56bright and CD56dim, 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 CD56bright, 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 (β = −0.506, P = .003) and CD56dim/CD56bright cell (β = −.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 CD56dim/CD56bright cells by day 14 after HSCT (β = −0.474, P = .005). Moreover, the dose of CD56dim NK cells in the allograft was positively associated with the day 14 CD56brigh NK cells (β = 0.494, P = .032) and inversely correlated with the day 14 ratio of CD56dim/CD56bright cells (β = −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 CD56bright 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.