Disturbed Sleep in Pediatric Patients With Leukemia: The Potential Role of &lt;i&gt;Interleukin-6&lt;/i&gt; (-174GC) and &lt;i&gt;Tumor Necrosis Factor&lt;/i&gt; (-308GA) Polymorphism

Vallance, Kelly; Yang, Jie; Jiang, Li; Crabtree, Valerie McLaughlin; Hinds, Pamela S.; Mandrell, Belinda N.

doi:10.1188/11.onf.e365-e372

Cited by 21 publications

(17 citation statements)

References 38 publications

(48 reference statements)

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“…Such changes to sleep architecture may be responsible for the subjective experience of poor sleep quality and reports of increased awakenings. Older patient age and higher risk group have also been shown to contribute to slower dexamethasone clearance, which may contribute to some of the variabilities observed within steroid groups in the current study [40]. …”

Section: Discussionmentioning

confidence: 99%

The impact of dexamethasone and prednisone on sleep in children with acute lymphoblastic leukemia

Daniel

Kloss

et al. 2016

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Purpose Corticosteroids can affect sleep patterns, mood, and behavior. Two of the most commonly prescribed corticosteroids in acute lymphoblastic leukemia (ALL), dexamethasone and prednisone, may impact sleep differently, but no research has compared these medications in children. The current study tested the hypothesis that dexamethasone and prednisone differentially affect sleep in children with ALL to understand how these medications contribute to health-related quality of life (HRQL). Methods Parents of 81 children 3–12 years old in maintenance therapy for ALL completed a baseline measure of child sleep (dexamethasone n = 55, prednisone n = 26), and 61 parents returned 28 days of child sleep diaries starting the first day of a 5-day steroid course (dexamethasone n = 43, prednisone n = 18). Parents also completed measures of HRQL and fatigue on the last day of steroids and the last day of the month. Results At baseline, parents reported more sleep disturbances in children taking dexamethasone than prednisone. Across the month, children taking dexamethasone experienced poorer sleep quality compared to children taking prednisone. During corticosteroid treatment, children taking dexame thasone also experienced more night awakenings than children taking prednisone. Sleep variables accounted for almost half of the variance in HRQL during time off steroids and also significantly contributed to fatigue during the corticosteroids course and time off corticosteroids. Conclusions Sleep is an essential component of HRQL in children taking corticosteroids, and the impact on sleep is more pronounced in children taking dexamethasone compared to prednisone. Screening for sleep disturbances and offering brief interventions to manage steroid-related sleep disruptions may improve HRQL.

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Section: Discussionmentioning

confidence: 99%

The impact of dexamethasone and prednisone on sleep in children with acute lymphoblastic leukemia

Daniel

Kloss

et al. 2016

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“…[39, 40] In studying this relationship in children undergoing steroid chemotherapy for ALL, Vallance, et al found a correlation between a polymorphism in the TNF gene (-308G>A) and steroid-associated sleep disruption. [41] In our study and presented in supporting information, we also investigated the effect of dexamethasone on melanin-concentrating hormone (MCH), an influential regulator of the ascending arousal system that controls the switch from REM sleep to NREM sleep; we found no evidence that dexamethasone affects MCH physiology (S1 Supplemental Methods, S1 Supplemental Results and S3 Fig). …”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Chemotherapy Does Not Disrupt Orexin Signaling

et al. 2016

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BackgroundSteroid-induced sleep disturbance is a common and highly distressing morbidity for children receiving steroid chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL). Sleep disturbance can negatively impact overall quality of life, neurodevelopment, memory consolidation, and wound healing. Hypothalamic orexin neurons are influential wake-promoting neurons, and disturbances in orexin signaling leads to abnormal sleep behavior. A new class of drug, the orexin receptor antagonists, could be an intriguing option for sleep disorders caused by increased orexinergic output. Our aim was to examine the impact of ALL treatment doses of corticosteroids on the orexin system in rodents and in children undergoing treatment for childhood ALL.MethodsWe administered repeated injections of dexamethasone to rodents and measured responsive orexin neural activity compared to controls. In children with newly diagnosed standard risk B-cell ALL receiving dexamethasone therapy per Children’s Oncology Group (COG) induction therapy from 2014–2016, we collected pre- and during-steroids matched CSF samples and measured the impact of steroids on CSF orexin concentration.ResultsIn both rodents, all markers orexin signaling, including orexin neural output and orexin receptor expression, were preserved in the setting of dexamethasone. Additionally, we did not detect a difference in pre- and during-dexamethasone CSF orexin concentrations in children receiving dexamethasone.ConclusionsOur results demonstrate that rodent and human orexin physiology is largely preserved in the setting of high dose dexamethasone. The data obtained in our experimental model fail to demonstrate a causative role for disruption of the orexin pathway in steroid-induced sleep disturbance.

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“…They are noted to be increased in adults and children with obstructive sleep apnea and sleep insufficiency, and they are associated with daytime sleepiness. TNF-α and IL-1 meet the criteria as sleep-regulatory substances [24]. Single-nucleotide polymorphisms of TNF-α and IL-6 are associated with disturbed sleep in children with ALL [25].…”

Section: Discussionmentioning

confidence: 99%

The effects of Dexamethasone on sleep in young children with Acute Lymphoblastic Leukemia

et al. 2015

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Purpose Corticosteroids, which are a mainstay in the treatment of acute lymphoblastic leukemia (ALL), have a well-documented adverse effect on sleep. We sought to characterize the effects of dexamethasone on sleep over an entire 28-day treatment cycle using actigraphy, an objective measure of sleep. Methods The sleep of 25 children aged 2–9 years (mean 4.5 years) with ALL treated with dexamethasone were evaluated during maintenance chemotherapy using a within-subject experimental design, actigraphy, and standardized questionnaires to assess sleep, sleep problems, and fatigue. Results During the five days of dexamethasone treatment, sleep time increased during the night (535 vs. 498 min; p = 0.004) and daytime napping increased the following day (14 vs. 0 min; p = 0.002), and the number of wake episodes during the night was lower (14 vs. 20; p = ≤ 0.001). However, when assessed individually, sleep-onset time, efficiency, and wake after sleep onset during the night were unchanged during dexamethasone treatment; when the cumulative effect of all of these factors was assessed, there was a statistically and clinically significant increase in nighttime sleep duration during dexamethasone treatment. Conclusions During the five days of treatment with dexamethasone, an increase in nighttime sleep as well as daytime napping was observed in young children with ALL. The increases in sleep duration return to baseline one day after the discontinuation of dexamethasone.

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Disturbed Sleep in Pediatric Patients With Leukemia: The Potential Role of <i>Interleukin-6</i> (-174GC) and <i>Tumor Necrosis Factor</i> (-308GA) Polymorphism

Abstract: Disturbed sleep among pediatric patients with cancer is multifactoral and includes interactions among environment, medications, and genotype. Additional research should explore serum proinflammatory cytokine levels and the influence of mood and worry on sleep.

Cited by 21 publications

References 38 publications

The impact of dexamethasone and prednisone on sleep in children with acute lymphoblastic leukemia

The impact of dexamethasone and prednisone on sleep in children with acute lymphoblastic leukemia

Dexamethasone Chemotherapy Does Not Disrupt Orexin Signaling

The effects of Dexamethasone on sleep in young children with Acute Lymphoblastic Leukemia

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