Sex-specific associations between chemotherapy, chronic conditions and neurocognitive impairment in ALL survivors: A report from the Childhood Cancer Survivor Study

Abstract

Background

The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only.

Methods

This cross-sectional study included 1,207 ALL survivors (54.0% female; mean age 30.6 years) and 2,273 siblings (56.9% female; mean age 47.6 years), who completed the CCSS Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were two-sided.

Results

Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs. 16.9%; adjusted odds ratio [OR]=1.89, 95% confidence interval [CI]=1.31 to .74; females: 12.5% vs. 17.6%; OR = 1.50, 95% CI = 1.07to2.14), as well as impaired memory (males: 11.6% vs. 19.9%, OR = 1.89, CI = 1.31to2.74; females: 14.78% vs. 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), while impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92).

Conclusion

Neurocognitive impairment is associated with methotrexate, dexamethasone and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship.