Sex-Specific Associations Between Chemotherapy, Chronic Conditions, and Neurocognitive Impairment in Acute Lymphoblastic Leukemia 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.

Neurocognitive and Behavioral Outcomes of Chinese Survivors of Childhood Lymphoblastic Leukemia

“…Notably, these chronic health conditions were associated with worse outcomes on multiple self-reported behavioral measures, even after accounting for CRT status. This finding is similar to those of emerging studies that identified the contributions of chronic health conditions resulting from childhood cancer therapies to emotional distress and neurocognitive impairment (22,23,25). These observations have important clinical implications.…”

“…The severity of the conditions was graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE version 4.03) (41), which defines the severity of the health conditions as asymptomatic/mild symptoms (grade 1), moderate symptoms requiring minimal interventions (grade 2), severe/disabling symptoms requiring extensive interventions (grade 3), and life-threatening conditions (grade 4). For this study, the health conditions of interest were limited to the cardiopulmonary, endocrine, metabolic, psychiatric, neurological and hearing/vision systems, as these have been associated with neurocognitive function in cancer survivors (15,22,23,25,42). Only chronic health conditions with a reported age of onset during or after the completion of cancer treatment were included.…”

“…After treatment, aging survivors of childhood cancer develop chronic health conditions, such as cardiovascular, pulmonary and metabolic disorders, at higher rates than those observed in age-matched non-cancer siblings (20,21). In addition to their associations with early mortality, emerging studies of survivors have shown that these chronic health problems are related to cognitive impairment and psychosocial difficulties (15,(22)(23)(24)(25).…”

Survival in Patients with Acute Lymphoblastic Leukemia and COVID-19 in Mexico

“…The study consisted of 20 patients, of which eight (33.3%) were women, between 16 and 50 years old, with an average age of 37.75 ± 11.63 years and 12 men (66.7%) with a mean age of 28.50 ± 18.05 years, this range between 15 and 64 years, coincide with other authors, who indicate that men have a higher incidence, in acute lymphoblastic leukemia [10]. Seven patients presented comorbidities, without statistical association with sex (p = 0.370) (Table 1).…”

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients

“…Studies investigating the neurocognitive consequences of chemotherapy during childhood (see Figure 1 ) have also found impairments to working memory and executive function [ 20 , 67 , 68 , 69 ], as well as processing speed, task efficiency, attention, memory and learning [ 70 , 71 , 72 ]. An important association has been made between these functions and self-regulatory behaviour, such as effective coping [ 73 ].…”