Abstract
Natural killer (NK) cells are among the first lymphocytes to recover following allogeneic hematopoietic stem cell transplantation (HSCT). Their levels may reflect both homeostatic and inflammatory processes. In this study we analyzed the early reconstitution of NK cells in fifty-one patients with hematologic malignancies after a reduced-intensity regimen consisting of fludarabine and cyclophosphamide and its relationship to the development of acute graft-versus-host disease (aGVHD) and cytomegalovirus (CMV) reactivation.
NK cells were severely depleted by the fludarabine-cyclophosphamide conditioning regimen. On the day of the transplant, the NK levels had been reduced in all patients to 0 cells/microliter. Subsequent NK cell recovery was rapid. By two weeks post-transplant NK cells had recovered to median levels comparable those in the original hosts (median= 119 cells/microliter; range, 0–816) and by four weeks increased to a median of 161 cell/microliter (range, 6–701; p< 0.0001) as compared to pre-transplant levels. By the second month post-transplant the median levels decreased and were maintained at pre-transplant levels.
CMV antigenemia developed in 23 of the 51 patients at a median of 30 days post transplant (range, 20–213 days). The median NK cell reconstitution at 2 weeks in the patients who subsequently developed CMV antigenemia was 158 cells/microliter (range, 2–816) and was higher than that among patients without CMV antigenemia (median 71 NK cells/microliter, range 10–228;Wilcoxon rank sum test p = 0.05).
Grade I to III aGVHD developed in 31 out of 51 patients (median time = 27 days; range, 11–92 days). The NK cell levels in the patients who developed aGVHD were significantly higher at two weeks post-transplant (median NK = 193 cells/microliter; range, 0–816) than those in the patients who did not (median NK = 66 cells/microliter; range 2–215) (p = 0.005 by Wilcoxon rank sum test). Furthermore, based on a Kaplan-Meier analysis of time to aGVHD as a function of the NK levels at two weeks post-transplant, patients who had NK cell counts greater than 195 cells/microliter at two weeks post transplant had a significantly higher probability of developing aGVHD (p = 0.0036 by log-rank test) Figure 1.
These results suggest that the early NK cell reconstitution may serve as a biomarker of transplant outcomes, especially in predicting the development of acute GVHD.
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Disclosure: No relevant conflicts of interest to declare.
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