Contribution of Fatigue to Cognitive Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors

Abstract

Late effects such as neurocognitive issues and fatigue have been reported in childhood acute lymphoblastic leukemia (cALL) survivors. Yet, their association is often poorly understood. In this study, we wished to (1) describe neurocognitive difficulties and fatigue in a well-characterized cohort of long-term cALL survivors and (2) explore the risk of having neurocognitive deficits as a function of fatigue. Childhood ALL survivors (N = 285) from three Canadian treatment centers completed the DIVERGT battery of cognitive tests and the PedsQL Multidimensional Fatigue Scale. We performed logistic regressions to assess the risk of a survivor to show cognitive deficits (<2.0 SD) depending on their fatigue levels. At least one cognitive deficit on the DIVERGT was present in 31% of participants. Domains primarily affected were working memory, fine motor skills, and verbal fluency. Sleep/rest fatigue in youths was higher than norms (d = 0.35). The risk for cognitive deficits increased independently with levels of fatigue in the domains of cognitive speed and flexibility, working memory, and verbal fluency. For every 10-point increase on general or sleep/rest fatigue on the 0-100 scale, there was a median +23–35% risk of showing a deficit among the 7 tasks significantly associated with fatigue. Fatigue may constitute a complementary target when searching to mitigate cognitive issues in this population.

Keywords:

• Childhood acute lymphoblastic leukemia
• cognitive deficits
• fatigue
• neurocognitive late effects
• survivors

Acknowledgments

The team would like to thank all those involved directly or indirectly in the implementation of the PETALE project from which this study stems. This includes the participants, researchers, and support personnel.

Disclosure statement

The authors report there are no competing interests to declare.

Authors’ contribution

Study design: AM, SL, MK, CL, PR, DS, SS

Data collection: SL, CL, SM, BM, ER, DS, SS

Data analysis: AM, SL, SM, BM, PR, SS

Interpretation: AM, SL, CL, SM, BM, PR, ER, DS, SS

Manuscript writing: AM, SL, MK, CL, SM, BM, PR, ER, DS, SS

Data availability statement

The full dataset is available here: https://doi.org/10.5683/SP3/WLAHQQ.

Additional information

Funding

This work was supported by the Institute of Cancer Research of the Canadian Institutes of Health Research, in collaboration with C17 Council, Canadian Cancer Society, Cancer Research Society, Garron Family Cancer Centre at the Hospital for Sick Children, Ontario Institute for Cancer Research, Fonds de Recherche du Québec-Santé Cancer Grant, and Pediatric Oncology Group of Ontario grant number TCF 118694.