Cheung Yin Ting, Brinkman Tara M, Mulrooney Daniel A, Mzayek Yasmin, Liu Wei, Banerjee Pia, Panoskaltsis-Mortari Angela, Srivastava Deokumar, Pui Ching-Hon, Robison Leslie L, Hudson Melissa M, Krull Kevin R
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Cancer. 2017 Sep 1;123(17):3410-3419. doi: 10.1002/cncr.30742. Epub 2017 Apr 27.
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.
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.
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.
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.
儿童急性淋巴细胞白血病（ALL）的长期存活者存在神经认知功能障碍的风险，这可能与疲劳、睡眠问题、全身炎症和氧化应激有关。我们仅对接受化疗的儿童ALL存活者中的这些关联进行了研究。
儿童ALL存活者（男性35例，女性35例；平均年龄14.3岁[标准差4.7岁]，自诊断起的平均年限7.4年[标准差1.9年]）在诊断后5年完成神经认知测试、行为评分，并报告睡眠质量和疲劳症状。同时采集血清，检测白细胞介素（IL）-1β、IL-6、肿瘤坏死因子α（TNF-α）、高敏C反应蛋白（hsCRP）、丙二醛、髓过氧化物酶和氧化型低密度脂蛋白。采用一般线性模型评估生物标志物与功能结局之间的关联，并对年龄进行校正，按性别分层。
存活者在执行功能和处理速度方面的表现低于人群常模，并报告有更多行为问题（经多重比较校正后P <.05）。在女性存活者中，疲劳与较差的执行功能（r = 0.41；P = .02）、处理速度（r = 0.56；P <.001）和注意力（r = 0.36 - 0.55；P <.05）相关。夜间频繁醒来的女性存活者表现出更多注意力不集中（P = .01）、多动（P = .03）和攻击行为（P = .01）。IL-6、IL-1β和hsCRP水平较高的女性存活者表现出更差的执行功能、处理速度和行为症状（P <.05）。TNF-α水平较高的男性存活者表现出更差的组织能力（P = .03），但未观察到神经认知结局与睡眠/疲劳指标之间的显著关联。
儿童ALL女性存活者的神经认知功能似乎更容易受到睡眠障碍和疲劳的影响。全身炎症可能在神经认知障碍和行为症状中起作用。癌症2017；123：3410 - 9。©2017美国癌症协会。
