Children treated for acute lymphocytic leukemia (ALL) receive central nervous system–directed chemotherapy, which is a known risk factor for cognitive dysfunction. ALL chemotherapy treatment is also associated with changes in biomarkers of inflammation and oxidative stress, which may underlie changes in neurocognitive functioning.
F2-isoprostanes is a biomarker of oxidative stress and interleukin-8 (IL-8) is an inflammatory cytokine. Both of these cerebrospinal fluid (CSF) markers have been associated with the severity of a symptom cluster in children with ALL. The purpose of this study was to explore relationships between CSF biomarkers of oxidative stress and inflammation and cognitive function of children during the final phase of ALL therapy (maintenance). In this repeated-measures design, F2-isoprostanes and IL-8 were evaluated in CSF samples collected in children age 4–19 years at the beginning and end of ALL maintenance therapy. Child- and parent-reported measures of cognitive function were completed at these same time-points. Children completed the NIH Toolbox® Flanker and card sorting cognitive measures at the end of maintenance. Among study participants (n = 30), IL-8 levels decreased (p < .01) and parent report of their child’s cognition improved (p = .02). At the end of maintenance, mean Flanker scores were more than 1 SD below the norm; higher F2-isoprostane levels were associated with lower Flanker scores (p < .05). Children who were >1 SD below the mean on Flanker test at the end of maintenance (n = 14) had significantly higher F2-isoprostane levels at both time-points (p < .01; p = .02). F2-isoprostane may be a useful biomarker for cognitive dysfunction in children with ALL and merits further investigation. Earlier identification of these children would allow for early, individualized interventions to improve cognitive outcomes during treatment and long-term survival.
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- Casey Hooke, PhD APRN PCNS FAAN CPON®
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