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

Yin Ting Cheung, Tara M. Brinkman, Daniel A. Mulrooney, Yasmin Mzayek, Wei Liu, Pia Banerjee, Angela Panoskaltsis-Mortari, Deokumar Srivastava, Ching Hon Pui, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3410-3419
Number of pages10
Issue number17
StatePublished - Sep 1 2017

Bibliographical note

Publisher Copyright:
© 2017 American Cancer Society


  • behavioral
  • childhood acute lymphoblastic leukemia
  • fatigue
  • inflammation
  • neurocognitive
  • oxidative stress
  • sleep
  • survivorship


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