Year: 2026
Type: article
Study design: Systematic Review
Abstract: Methotrexate (MTX) is widely used in the treatment of acute lymphoblastic leukemia (ALL) in children but is associated with neurotoxic effects, including leukoencephalopathy (LE). These effects can profoundly affect quality of life and neurocognitive development. We conducted a literature review across multiple databases between 2014 and 2024. The study population included children and adolescents with cancer (under 22 years old) treated with MTX, focusing on LE. Case reports, case series, and reviews were excluded. We analyzed factors such as age, dose, and route of administration (intrathecal or intravenous), correlating clinical and imaging data with neurocognitive outcomes. We included 12 of the 262 identified studies. Most studies involved survivors of childhood cancer diagnosed with ALL (n = 11). LE presented heterogeneously, with clinical manifestations such as seizures, focal neurological deficits, and subtle cognitive declines, particularly in working memory and processing speed. A substantial portion of the lesions persisted even after treatment completion, emphasizing the link between white matter microstructural changes and MTX use. Results indicated that the combination of age and cumulative dose acted as the primary determinant of vulnerability. MTX-induced LE is a significant clinical challenge. Early detection and longitudinal monitoring are crucial to minimize neurocognitive impacts in pediatric survivors. Future research should focus on strategies to mitigate neurotoxicity and optimize quality of life for ALL survivors.
Source: Brazilian Journal of Oncology
Institution: Universidade Estadual Paulista (Unesp)
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7170804886