Association between fatigue and sleep disturbances during treatment for pediatric acute lymphoblastic leukemia and posttreatment neurocognitive performance

Abstract

Background: Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk of neurocognitive weakness in the areas of attention, executive function, and processing speed. Although fatigue and sleep disturbances are frequent complications of ALL therapy and associated with cognitive functions, the impact of fatigue and sleep profiles during active ALL treatment on posttreatment neurocognitive performance has received limited attention. Methods: Pediatric patients (n = 120) with ALL (diagnosed 2011-2016) who completed fatigue and sleep questionnaires at four time points during active treatment were enrolled in a study of neurocognitive performance. Latent class growth analysis identified subgroups of patients with similar sleep and fatigue profiles during treatment. Neurocognitive performance collected >6 months post treatment on 40 participants was compared between latent classes using multivariable linear regression models. Results: Participants (57.5% male and 79.1% Hispanic or non-Hispanic White) were classified into one of two fatigue and sleep profiles: Class 1 characterized by mild fatigue and sleep disturbances during treatment (50.8%), and Class 2 characterized by higher levels of fatigue and sleep disturbances (49.2%). Posttreatment cognitive performance was in the normal range for most measures, but significantly below normative means for executive function, verbal short-term memory, attention, and distractability measures. Compared to Class 1, Class 2 demonstrated significantly (p < .05) poorer posttreatment neurocognitive performance, particularly in measures of attention. Conclusions: Our findings indicate that fatigue and sleep disturbances during the first year of pediatric ALL therapy may impact long-term neurocognitive performance.

Insomnia Symptoms and Daytime Fatigue Co-Occurrence in Adolescent and Young Adult Childhood Cancer Patients in Follow-Up after Treatment: Prevalence and Associated Risk Factors

“…Those with both insomnia symptoms and daytime fatigue also reported more severe insomnia symptoms than those with insomnia only, which is in line with the previous literature [ 47 ]. The subgroup with co-occurring insomnia–daytime fatigue might be a more vulnerable patient group for poorer health outcomes for various reasons: (1) co-morbid health problems were more common in this group, which is also in line with previous insomnia research [ 48 ]; (2) in the general population, having insomnia and fatigue was related to more impaired health-related quality of life than those with less symptoms [ 9 ], and (3) in a cohort of non-irradiated pediatric acute lymphoblastic leukemia survivors, the cluster with more severe fatigue and sleep problems had more neurocognitive deficiency than those with milder symptoms [ 28 ]. Furthermore, insomnia and daytime fatigue might overall also cluster with several psychological complaints that have been reported by survivors, such as depression and anxiety [ 49 ], which has also been found in the general population [ 50 ].…”

“…(2) in the general population, having insomnia and fatigue was related to more impaired health-related quality of life than those with less symptoms [9], and (3) in a cohort of nonirradiated pediatric acute lymphoblastic leukemia survivors, the cluster with more severe fatigue and sleep problems had more neurocognitive deficiency than those with milder symptoms [28]. Furthermore, insomnia and daytime fatigue might overall also cluster with several psychological complaints that have been reported by survivors, such as depression and anxiety [49], which has also been found in the general population [50].…”

“…However, in a study of 62 long-term survivors of childhood lymphomas and leukemia, 59% of those with persistent chronic fatigue had insomnia versus 21% in non-fatigued survivors [ 26 ]. In addition, some studies after treatment did report a correlation between sleep and fatigue [ 27 ], sleep–fatigue symptom clusters [ 28 ], or found sleep disturbance as a predictor of fatigue [ 29 ]. In adult oncology, an interrelationship between impaired sleep and fatigue in survivors using different methods and in diverse populations has been reported [ 30 , 31 , 32 ]; however, much remains unclear about the specific mechanisms of co-occurring insomnia and fatigue.…”

Impaired neurocognitive functioning 3 months following diagnosis of high‐risk acute lymphoblastic leukemia: A report from the Children's Oncology Group

“…Fatigue has been systematically examined in survivors of pediatric cancer only recently, and findings have varied depending on how, when, and by whom symptoms are reported. 29,[37][38][39] As the early phase of ALL treatment is intensive, many children have difficulty tolerating comprehensive neuropsychological assessments.…”

“…This could reflect shared neurophysiological mechanisms (e.g., neuroinflammation) underlying both fatigue and impaired cognition, 36 or the impact of chronic fatigue on cognition over time. Fatigue has been systematically examined in survivors of pediatric cancer only recently, and findings have varied depending on how, when, and by whom symptoms are reported 29,37–39 …”