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Updated: Aug 18, 2026
Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
Cognitive changes in children treated for acute lymphoblastic leukemia with chemotherapy only according to the
Isabelle Montour-Proulx1, Sally M Kuehn, Daniel L Keene
1Oncology/Medical Day Patient Service Unit Children's Hospital of Eastern Ontario, Ottawa, ON. montour@cheo.on.ca
Insights
Children treated for leukemia showed low-average cognitive function and memory. Higher doses of intrathecal methotrexate correlated with declining performance IQ and increased neurotoxicity risk.
Area of Science:
- Pediatric Oncology
- Neuroscience
- Neuropsychology
Background:
- Childhood leukemia treatment can impact cognitive development.
- Neuroimaging may reveal treatment-related brain changes.
Purpose of the Study:
- To assess cognitive function and neuroimaging findings in children with leukemia.
- To investigate the relationship between treatment protocols and neurotoxicity.
Main Methods:
- Assessed cognitive functioning using Wechsler scales (IQ, memory).
- Analyzed neuroimaging (MRI) for leukoencephalopathy.
- Correlated treatment variables (e.g., intrathecal methotrexate dosage) with outcomes.
Main Results:
- Children scored in the low-average range for IQ and memory.
- Wechsler Performance IQ declined significantly over time.
- Cumulative intrathecal methotrexate dosage adversely affected Performance IQ.
- Leukoencephalopathy was prevalent (78%) on MRI, often without seizures.
Conclusions:
- Cognitive deficits and neurotoxicity are significant concerns in childhood leukemia survivors.
- Intrathecal methotrexate dose is a risk factor for cognitive decline.
- Seizures are unreliable indicators of neurotoxicity; MRI is crucial for detection.
Abstract:
The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Children's Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 +/- 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 +/- 15.69 and 84.83 +/- 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 +/- 15.46 and 88.30+/- 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity.