Trajectory of Neurocognitive Functioning in Children Treated for Acute Lymphoblastic Leukemia (ALL): Dana-Farber Cancer Institute ALL Consortium Study 16-001

Background: Children treated for acute lymphoblastic leukemia (ALL) are at risk of neurocognitive deficits in attention-concentration, working memory, executive function, and psychomotor speed. Objectives: This study evaluated longitudinal trajectories and medical/demographic associations with neurocognitive outcomes during treatment of newly diagnosed ALL. Methods: Patients ages 3–21 treated on DFCI 16-001 (NCT03020030) across eight North American sites (2017–2022) were evaluated using Cogstate across four timepoints from diagnosis through maintenance phase. Linear mixed models estimated trajectories and interactions with clinical factors over time, incorporating random effects for patients and sites. Results: Among 298 patients (median age 7.9 years, 53% male), performance changed significantly over time in varying directions for executive functioning, attention, visual learning, and working memory-accuracy (all p < 0.001). There was a significant interaction overall between age and time for psychomotor function (interaction p = 0.01) and working memory-accuracy (interaction p < 0.001). Older age was associated with worse performance on working memory-speed (β = −0.04) and attention (β = −0.05). Female sex was associated with worse performance on psychomotor function (β = −0.27) and working memory-accuracy (β = −0.50), but better on visual learning (β = 0.47) and working memory-speed (β = 0.30). A greater-than-expected proportion of participants performed below −1.5 SD on tests of attention, executive functioning, and psychomotor functioning at multiple timepoints. Conclusions: While most patients demonstrated normal neurocognitive functioning, including variable trajectories, a subgroup performed poorly on attention, executive functioning, and psychomotor functioning. Risk factors include older age at diagnosis and female sex, which may provide insight into groups warranting early intervention.