TY - JOUR
T1 - Impact of sleep, fatigue, and systemic inflammation on neurocognitive and behavioral outcomes in long-term survivors of childhood acute lymphoblastic leukemia
AU - Cheung, Yin Ting
AU - Brinkman, Tara M.
AU - Mulrooney, Daniel A.
AU - Mzayek, Yasmin
AU - Liu, Wei
AU - Banerjee, Pia
AU - Panoskaltsis-Mortari, Angela
AU - Srivastava, Deokumar
AU - Pui, Ching Hon
AU - Robison, Leslie L.
AU - Hudson, Melissa M.
AU - Krull, Kevin R.
N1 - Publisher Copyright:
© 2017 American Cancer Society
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - behavioral
KW - childhood acute lymphoblastic leukemia
KW - fatigue
KW - inflammation
KW - neurocognitive
KW - oxidative stress
KW - sleep
KW - survivorship
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U2 - 10.1002/cncr.30742
DO - 10.1002/cncr.30742
M3 - Article
C2 - 28452142
AN - SCOPUS:85018939581
SN - 0008-543X
VL - 123
SP - 3410
EP - 3419
JO - Cancer
JF - Cancer
IS - 17
ER -