| Sumario: | Purpose: Survivors of childhood acute lymphoblastic leukemia (ALL) treated with CNS-directed chemotherapy are at risk for neurocognitive deficits. Prospective longitudinal studies are needed to clarify the neurodevelopmental trajectory in this vulnerable population. Methods: Patients enrolled in the St. Jude Total Therapy Study XV, which omitted prophylactic cranial radiation therapy in all patients, completed comprehensive neuropsychological assessments at induction (n = 142), end of maintenance (n = 243), and 2 years after completion of therapy (n = 211). We report on longitudinal change in neurocognitive function and predictors of neurocognitive outcomes 2 years after completing therapy. Results: Neurocognitive function was largely age appropriate 2 years after completing therapy; however, the overall group demonstrated significant attention deficits and a significantly greater frequency of learning problems as compared with national normative data (all P ≤ .005). Higher-intensity CNS-directed chemotherapy conferred elevated risk for difficulties in attention, processing speed, and academics (all P ≤ .01). The rate and direction of change in performance and caregiver-reported attention difficulties differed significantly by age at diagnosis and sex. End-of-therapy attention problems predicted lower academic scores 2 years later, with small to moderate effect sizes (│r│= 0.17 to 0.25, all P ≤ .05). Conclusion: Two years after chemotherapy-only treatment, neurocognitive function is largely age appropriate. Nonetheless, survivors remain at elevated risk for attention problems that impact real-world functioning. Attention problems at the end of therapy predicted decreased academics 2 years later, suggesting an amplified functional impact of discrete neurocognitive difficulties. Age at diagnosis and patient sex may alter neurocognitive development in survivors of childhood ALL treated with chemotherapy-only protocols.
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