Postacute Neurocognitive Sequelae Following Pediatric Chemotherapy: A Retrospective Study From the Montefiore Survivorship Clinic (2000-2024).

Abstract

Standard neurocognitive and imaging assessments in research settings may not fully capture the real-world symptom burden experienced by pediatric hematologic cancer survivors. We conducted a retrospective analysis using electronic medical record data to evaluate cognitive and imaging findings as well as comorbidities in this patient population. We retrospectively reviewed data from 314 pediatric blood cancer survivors (diagnosed at age ≤21) followed at the Montefiore Survivorship Clinic between 2000 and 2024. Neurocognitive assessments, neuroimaging, and treatment exposures were extracted. The chi-square test was used for group comparison of categorical variables, and the independent t-test was used for group comparison of continuous variables. The risk of developing a neurocognitive complaint was assessed using a multivariable Cox-proportional hazards model. Neurocognitive complaints were documented in 56 of 314 patients (18%). Younger age at cancer diagnosis (adjusted hazard ratio [HR], 0.94 [0.88-0.99]; <i>P</i> = .03) and exposure to high-dose methotrexate (adjusted HR, 3.34 [1.67-6.67]; <i>P</i> < .005) were independently associated with increased risk of neurocognitive complaints. Neurocognitive testing revealed deficits across multiple domains, with most pronounced impairments in full-scale intelligence quotient (mean percentile: 27%) and verbal comprehension (mean percentile: 31%). Consistent neuroimaging abnormalities, including white matter changes and T2 hyperintensities, were observed in 25% of symptomatic patients, although most had unremarkable findings, suggesting underlying microstructural or functional disruptions undetected by standard imaging. Chemotherapy-related neurocognitive dysfunction affects nearly one in five pediatric hematologic cancer survivors, with younger age at diagnosis and methotrexate exposure as major risk factors.