Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia.

Abstract

Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid (CSF). Identification of acute declines in neurocognitive function, as well as predictive genotypes or biomarkers, could guide therapeutic trials of protective interventions. This study collects CSF while prospectively assessing neurocognitive functioning (working memory, executive function, learning, processing speed, and attention) of ALL patients using the Cogstate computerized battery at six time points during and after the 2years of leukemia treatment on a Dana-Farber Cancer Institute ALL Consortium trial. Baseline data collected during the first 3weeks of induction chemotherapy indicate reliable data as all subjects (N=34) completed Cogstate baseline testing, while completion and performance checks indicate that 100% of subjects completed testing and complied with test requirements. The majority (85%) exhibited normal function compared with age peers. Preliminary analysis of CSF biomarkers (folate, homocysteine, 8-isoprostane, and myelin basic protein) similarly reveals values at baseline within expected normal ranges. The first month of induction therapy for ALL is a reliable baseline for detecting treatment-induced changes in neurocognitive functioning. Consequently, serial data collection might identify subgroups of ALL patients at increased risk for neurocognitive decline, warranting proactive interventions to improve their level of functioning both during treatment and into survivorship.