ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 174 papers, 4 of them syntheses that pooled it.
What it found
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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.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
174 citing papers in PubMed, 4 syntheses or guidelines pooled it, 372 citations in OpenAlex.
- Mass spectrometry-based proteomics of cerebrospinal fluid in pediatric central nervous system malignancies: a systematic review with meta-analysis of individual patient data.Fluids and barriers of the CNS · 2024Pooled it
- Monitoring Neurocognitive Functioning After Pediatric Cellular Therapy or Hematopoietic Cell Transplant: Guidelines From the COG Neurocognition in Cellular Therapies Task Force.Transplantation and cellular therapy · 2022Guideline
- Genetic Modulation of Neurocognitive Development in Cancer Patients throughout the Lifespan: a Systematic Review.Neuropsychology review · 2019Pooled it
- Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review.Neuroscience and biobehavioral reviews · 2015Pooled it
- Trial
- Successful Outcomes of Newly Diagnosed T Lymphoblastic Lymphoma: Results From Children's Oncology Group AALL0434.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children's Oncology Group Study AALL1131.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Reduced brain microstructural asymmetry in patients with childhood leukemia treated with chemotherapy compared with healthy controls.PloS one · 2019Trial
- Trial
- Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children's Oncology Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Trial
- Cancer therapy-related cognitive impairment, part 1: an integrative clinical-mechanistic framework from phenotypes to convergent neurobiological pathways.Pharmacological reports : PR · 2026Review
- Severe Brain Atrophy after Allogeneic Hematopoietic Stem Cell Transplantation in a Patient Suffering from Chronic Graft-versus-host Disease.Internal medicine (Tokyo, Japan) · 2026Article
- Phenotype-Specific Pharmacogenetic Patterns of Methotrexate Neurotoxicity in Pediatric Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2026Article
- Mitochondrial Genomic Alterations in Pediatric Acute Lymphoblastic Leukemia: Implications for Methotrexate-Induced Neurotoxicity and Ethnic Disparities.Cancer medicine · 2026Article
- Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.Nature cancer · 2026Article
- Central nervous system involvement and relapse in adult acute lymphoblastic leukaemia-a population-based analysis in 2007-2022.British journal of haematology · 2026Article
- Dysregulation of the inside-out signaling pathway in CNS-infiltrated pediatric T-cell acute lymphoblastic leukemia.Research square · 2026Article
- Cancer treatment-related cognitive impairment.Neuro-oncology advances · 2026Review
- Feasibility of Non-Sedated Multispectral Neuroimaging in Newly Diagnosed Children with Leukemia.medRxiv : the preprint server for health sciences · 2026Article
- Clinical and germline risk factors for multiple treatmentrelated toxicities in pediatric acute lymphoblastic leukemia.Haematologica · 2026Article
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
purposeMethotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. PATIENTS AND
methodsProspective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities.
resultsFourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity.
conclusionMTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.