Natural killer (NK) cells are associated with reduced relapse without increased graft-versus-host disease (GVHD) after allogeneic hematopoetic stem-cell transplantation (HSCT)

Abstract

6542 Background: Natural killer cells have potential for anti-leukemia activity after haplo-identical HSCT. However, the role of reconstituted NK cells in relapse and survival after matched HLA-identical HSCT is unknown. We investigated the correlation between NK reconstitution and death, relapse, and GVHD after HSCT. Methods: We prospectively studied NK reconstitution in 123 patients with predominantly high-risk hematologic malignancies. Peripheral blood absolute NK cell count (ANK) was determined by flow cytometry analysis of lymphocytes co-expressing bright staining CD56+ and CD16+. Cluster analysis distinguished patients at engraftment with high ANK (>12.2/mm3) (n=80) and low ANK (n=43), and at 60 days with high ANK (>20/mm3) (n=64) and low ANK (n=26). Primary study endpoints were death, relapse and acute grade II-IV GVHD with median follow up of 360 days (28–1967). A cox proportional hazard model was adjusted for important covariates, including age, transplant conditioning (myeloablative vs. non-myeloablative), graft source (peripheral blood vs. bone marrow), and donor-type (HLA-matched related vs. unrelated), dendritic cell level and absolute neutrophil count. Results: A low ANK at engraftment was significantly associated with death (p=0.03) after non-myeloablative HSCT. Using a selection model, only NK remained in the model, and a low ANK was associated with a 2.5 hazard ratio for subsequent death (p=0.04). Additionally, for the overall cohort, ANK at 60 days was strongly associated with time to death (92% in high vs 65% in low group; LR p=0.0007), at 310 days after HSCT. ANK level at 60 days was strongly associated with time to relapse (n=82, (LR p=0.0001). In a multivariate model, low ANK at 60 days was associated with a 4.2 fold relative risk (RR) of death (1.9, 9.1) and 8.6 RR for time to relapse (3.1, 24.3). Conclusions: High NK cell reconstitution is associated with reduced relapse and death without increased incidence of GVHD after HLA-identical HSCT. Our study suggests that NK may have both a potential anti-tumor effect, as well as be tolerogenic. Measuring NK after HSCT may have novel prognostic and therapeutic implications. No significant financial relationships to disclose.