Cognitive and behavioral risk factors for low quality of life in survivors of childhood acute lymphoblastic leukemia

Ellen van der Plas; T Leigh Spencer Noakes; Darci T Butcher; Rosanna Weksberg; Laura Galin-Corini; Elizabeth A Wanstall; Patrick Te; Laura Hopf; Sharon Guger; Johann Hitzler; Russell J Schachar; Shinya Ito; Brian J Nieman

doi:10.1038/s41390-020-01230-7

Cognitive and behavioral risk factors for low quality of life in survivors of childhood acute lymphoblastic leukemia

Pediatr Res. 2021 Aug;90(2):419-426. doi: 10.1038/s41390-020-01230-7. Epub 2020 Nov 17.

Authors

Ellen van der Plas¹, T Leigh Spencer Noakes^{2

3}, Darci T Butcher^{4

5}, Rosanna Weksberg^{4

6

7

8}, Laura Galin-Corini³, Elizabeth A Wanstall^{9

10}, Patrick Te^{3

11}, Laura Hopf⁹, Sharon Guger⁹, Johann Hitzler^{12

13

14}, Russell J Schachar^{15

16}, Shinya Ito^{3

11

17}, Brian J Nieman^{18

19

20

21}

Affiliations

¹ Department of Psychiatry, University of Iowa Hospital & Clinics, Iowa City, IA, USA.
² Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada.
³ Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Genetics & Genome Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
⁵ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Clinical and Metabolic Genetics, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
⁷ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁸ Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
⁹ Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁰ Department of Psychology, York University, Toronto, ON, Canada.
¹¹ Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, ON, Canada.
¹² Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹³ Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada.
¹⁴ Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
¹⁵ Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada.
¹⁶ Psychiatry Research, Hospital for Sick Children, Toronto, ON, Canada.
¹⁷ Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁸ Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada. brian.nieman@sickkids.ca.
¹⁹ Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada. brian.nieman@sickkids.ca.
²⁰ Ontario Institute for Cancer Research, Toronto, ON, Canada. brian.nieman@sickkids.ca.
²¹ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. brian.nieman@sickkids.ca.

Abstract

Background: With high survival rates for pediatric acute lymphoblastic leukemia (ALL), long-term quality of life is a prominent consideration in treatment. We concurrently evaluated cognition, behavior, and quality of life in child and adolescent ALL survivors and determined associations between them.

Methods: The sample included 83 controls (mean age: 12.5 years) and 71 ALL survivors (mean age: 11.9 years, mean age at diagnosis: 3.8 years). Participants completed measures of general intellectual abilities, math achievement, and fine motor skills. Parents and teachers completed a survey assessing child participants' cognitive, behavioral, and emotional function. Parents additionally completed a survey about their child's quality of life.

Results: Survivors had lower scores on measures of working memory, processing speed, timed math, and fine motor skills (effect size 0.5-1, p < 0.001). Parents identified more problems with executive function and learning in survivors than controls (effect size > 0.7, p < 0.001), and indicated a lower quality of life in all categories evaluated (effect size > 0.7, p < 10^-4). Reduced quality of life was associated with lower math achievement scores and with inattention and executive function problems.

Conclusions: ALL survivors experience diffuse cognitive, behavioral, and motor impairments, which are associated with reduced quality of life. These findings underscore the need to address these challenges in ALL survivors.

Impact: Compared with cancer-free peers, parents of childhood acute lymphoblastic leukemia survivors treated with chemotherapy only reported reduced quality of life. Math difficulties and behavioral problems increased the risk for reduced quality of life. Reduced quality of life is associated with mild cognitive and behavioral difficulties, suggesting that even relatively mild impairments have broad implications for ALL survivors. Screening and early intervention targeting cognitive and behavioral function may enhance quality of life for ALL survivors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adolescent Behavior*
Adolescent Development*
Age Factors
Cancer Survivors / psychology*
Case-Control Studies
Child
Child Behavior*
Child Development*
Child, Preschool
Cognition*
Emotions
Executive Function
Female
Humans
Intelligence
Male
Memory, Short-Term
Motor Skills
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
Quality of Life*
Risk Assessment
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding