Impact of sleep, fatigue, and systemic inflammation on neurocognitive and behavioral outcomes in long‐term survivors of childhood acute lymphoblastic leukemia

BACKGROUND Long‐term survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive impairment, which may be associated with fatigue, sleep problems, systemic inflammation, and oxidative stress. We examined these associations among survivors of childhood ALL treated with chemotherapy only. METHODS Survivors of childhood ALL (male, n = 35 and female, n = 35; mean age, 14.3 years [standard deviation, 4.7 years] and mean years from diagnosis, 7.4 years [standard deviation, 1.9 years]) completed neurocognitive testing, behavioral ratings, and reported sleep quality and fatigue symptoms 5 years after diagnosis. Serum was collected concurrently and assayed for interleukin (IL)‐1β and IL‐6, tumor necrosis factor α (TNF‐α), high‐sensitivity C‐reactive protein (hsCRP), malondialdehyde, myeloperoxidase, and oxidized low‐density lipoprotein. General linear modeling was used to assess associations among biomarkers and functional outcomes, adjusting for age and stratified by sex. RESULTS Survivors performed worse than population norms on executive function and processing speed and reported more behavioral problems (P < .05 adjusted for multiple comparison). In female survivors, fatigue was associated with poor executive function (r = 0.41; P = .02), processing speed (r = 0.56; P < .001), and attention (r = 0.36‐0.55; P < .05). Female survivors with frequent nighttime awakening displayed more inattention (P = .01), hyperactivity (P = .03), and aggression (P = .01). Worse executive function, processing speed, and behavioral symptoms were observed in female survivors with higher levels of IL‐6, IL‐1β, and hsCRP (P < .05). Male survivors with high levels of TNF‐α demonstrated worse organization (P = .03), but no significant associations between neurocognitive outcomes and sleep/fatigue measures were observed. CONCLUSION Neurocognitive function in female survivors of childhood ALL appears more susceptible to the effects of sleep disturbance and fatigue. Systemic inflammation may play a role in neurocognitive impairment and behavioral symptoms. Cancer 2017;123:3410‐9. © 2017 American Cancer Society. Female survivors of childhood acute lymphoblastic leukemia appear more susceptible to cognitive and behavioral effects of poor sleep and fatigue. Associations between inflammation and functional outcomes also differ by sex.