Neurocognitive Outcomes Decades After Treatment for Childhood Acute Lymphoblastic Leukemia: A Report From the St Jude Lifetime Cohort Study

TLDR

The study aimed to determine rates, patterns, and predictors of neurocognitive impairment in adults decades after childhood acute lymphoblastic leukemia treatment. A cohort of 567 survivors (mean age 33, mean time since diagnosis 26 years) was evaluated, with cranial radiation and chemotherapy doses abstracted and multivariable modeling performed to identify predictors of impairment. Neurocognitive impairment rates ranged from 28.6% to 58.9%, chemotherapy‑only survivors had higher impairment across domains, dexamethasone was associated with attention and executive dysfunction, cranial radiation effects depended on age, executive function risk increased with survival time in a dose‑dependent manner, behavior problems rose 5% per year, and impairment correlated with lower educational attainment and unemployment, highlighting persistent deficits in adult survivors.

Abstract

To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL).Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion.Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment.This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.