Sleep-wake rhythm disruption is associated with cancer-related fatigue in pediatric acute lymphoblastic leukemia

Lindsay M.H. Steur, Gertjan J.L. Kaspers, Eus J.W. Van Someren, Natasha K.A. Van Eijkelenburg, Inge M. Van der Sluis, Natasja Dors, Cor Van den Bos, Wim J.E. Tissing, Martha A. Grootenhuis, Raphaële R.L. Van Litsenburg

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STUDY OBJECTIVES: To compare sleep-wake rhythms, melatonin, and cancer-related fatigue in pediatric patients with acute lymphoblastic leukemia (ALL) to healthy children and to assess the association between sleep-wake outcomes and cancer-related fatigue. METHODS: A national cohort of ALL patients (2-18 years) was included. Sleep-wake rhythms were measured using actigraphy and generated the following variables: Interdaily stability (IS): higher IS reflects higher stability; intradaily variability (IV): lower IV indicates less fragmentation; L5 and M10 counts: activity counts during the five least and 10 most active hours, respectively; and relative amplitude (RA): the ratio of L5 and M10 counts (higher RA reflects a more robust rhythm). The melatonin metabolite, 6-sulfatoxymelatonin (aMT6s), was assessed in urine. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Using regression models sleep-wake rhythms, aMT6s, and cancer-related fatigue were compared to healthy children and associations between sleep-wake outcomes and cancer-related fatigue were assessed in ALL patients. RESULTS: In total, 126 patients participated (response rate: 67%). IS, RA, and M10 counts were lower in patients compared to healthy children (p < 0.001). aMT6s levels were comparable to healthy children (p = 0.425). Patients with ALL were more fatigued compared to healthy children (p < 0.001). Lower IS, RA and M10 counts and higher IV were significantly associated with more parent-reported cancer-related fatigue. Associations between sleep-wake rhythms and self-reported cancer-related fatigue were not statistically significant. CONCLUSIONS: Sleep-wake rhythm impairment is associated with more cancer-related fatigue in pediatric ALL patients. Interventions aimed to improve sleep hygiene and encourage physical activity may reduce cancer-related fatigue.

Original languageEnglish
Issue number6
Publication statusPublished - 15 Jun 2020


The research described in this article is supported by the Dutch Cancer Society (VU 2014-6703).

FundersFunder number
Dutch Cancer SocietyVU 2014-6703


    • actigraphy
    • acute lymphoblastic leukemia
    • cancer-related fatigue
    • children sleep–wake rhythms
    • physical activity


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