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Natural killer cells at day 15 (NK-15), after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT), is a prognostic factor for overall survival (OS) and progression-free survival (PFS) in non-Hodgkin lymphoma (NHL). The potential role of the immunologic (homeostatic) environment affecting NK-15 recovery and survival post-APHSCT has not been fully studied. Therefore, we evaluate prospectively the cytokine profile in 50 NHL patients treated with APHSCT. Patients with an interleukin-15 (IL-15)≥76.5 pg/mL at day 15 post-APHSCT experienced superior OS and PFS compared with those who did not; median OS; not reached versus 19.2 months, P<.002; and median PFS; not reached versus 6.8 months, P<.002, respectively. IL-15 was found to correlate with (rs=0.7, P<.0001) NK-15. Multivariate analysis showed only NK-15 as a prognostic factor for survival, suggesting that the survival benefit observed by IL-15 is most likely mediated by enhanced NK cell recovery post-APHSCT.