ArticleMolecular medicine (Cambridge, Mass.)2025
CSF metabolomic signature during therapy for childhood acute lymphoblastic leukemia predicts subsequent working memory impairment.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03020030 (Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents), which is not on this map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents
Who cites it
1 citing paper in PubMed.
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15 authors.
Funding
Abstract
backgroundAlthough typically curative, treatment for pediatric acute lymphoblastic leukemia (ALL) is associated with neurotoxicity and leads to chemotherapy-related cognitive impairment (CRCI) in 40–70% of survivors. Cerebrospinal fluid (CSF), which is routinely collected during intrathecal chemotherapy, offers a direct window into brain metabolism. This study characterizes longitudinal metabolic changes in the CSF of pediatric patients undergoing chemotherapy for ALL.
methodsCSF samples from 45 pediatric patients enrolled on the multi-institutional Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 16–001 were collected at five standardized timepoints over the first 20 weeks of treatment and analyzed using untargeted metabolomics. Cognitive outcomes were assessed post-treatment using age-appropriate Wechsler Intelligence scales, with the Working Memory Index (WMI) serving as the primary cognitive measure. Patients with WMI scores at least one standard deviation above (n = 21) or below (n = 24) the mean were selected for metabolomic comparison. This study constitutes an exploratory aim of the 16–001 clinical trial.
resultsOur analysis revealed a profound reorganization of the CSF metabolome during the first 18 days of treatment, spanning the induction phase of chemotherapy and early leukemia remission. This shift was characterized by alterations in amino acid, phospholipid, and one-carbon metabolism. Moreover, we identified a lipid-rich metabolomic signature predictive of low post-treatment WMI, implicating metabolic dysregulation in CRCI susceptibility.
conclusionsThese findings highlight the dynamic impact of chemotherapy on the CSF metabolome and support its utility as a matrix for monitoring neurotoxicity during pediatric ALL therapy. CSF metabolomics may enable the early identification of patients at risk for CRCI through predictive biomarkers and guide future neuroprotective interventions. Trial registration: Dana-Farber Cancer Institute ALL Consortium Protocol 16–001, clinicaltrials.gov ID NCT03020030; study start date 03/03/2017.
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