Genetic variants, neurocognitive outcomes, and functional neuroimaging in survivors of childhood acute lymphoblastic leukemia

Abstract Background Genetic predispositions may modulate risk for developing neurocognitive late effects in childhood acute lymphoblastic leukemia (ALL) survivors. Methods Long-term ALL survivors (n = 212; mean = 14.3 [SD = 4.77] years; 49% female) treated with chemotherapy completed neurocognitive...

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Bibliographic Details
Published in:JNCI cancer spectrum 2023-07, Vol.7 (4)
Main Authors: Gandy, Kellen, Sapkota, Yadav, Scoggins, Matthew A, Jacola, Lisa M, Koscik, Timothy R, Hudson, Melissa M, Pui, Ching-Hon, Krull, Kevin R, van der Plas, Ellen
Format: Article
Language:English
Subjects:
Female
Folic Acid - therapeutic use
Functional Neuroimaging
Glucocorticoids - therapeutic use
Humans
Male
Peptidylprolyl Isomerase - therapeutic use
Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Survivors
Tacrolimus Binding Proteins - therapeutic use
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Summary:Abstract Background Genetic predispositions may modulate risk for developing neurocognitive late effects in childhood acute lymphoblastic leukemia (ALL) survivors. Methods Long-term ALL survivors (n = 212; mean = 14.3 [SD = 4.77] years; 49% female) treated with chemotherapy completed neurocognitive testing and task-based functional neuroimaging. Based on previous work from our team, genetic variants related to the folate pathway, glucocorticoid regulation, drug metabolism, oxidative stress, and attention were included as predictors of neurocognitive performance, using multivariable models adjusted for age, race, and sex. Subsequent analyses evaluated the impact of these variants on task-based functional neuroimaging. Statistical tests were 2-sided. Results Survivors exhibited higher rates of impaired attention (20.8%), motor skills (42.2%), visuo-spatial memory (49.3%-58.3%), processing speed (20.1%), and executive function (24.3%-26.1%) relative to population norms (10%; P 
ISSN:2515-5091
2515-5091
DOI:10.1093/jncics/pkad039