Cited by 400Acute Lymphoblastic Leukemia researchGlioma Diagnosis and TreatmentCancer Treatment and Pharmacology

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Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia

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Bhojwani, Deepa, Sabin, Noah D., Pei, Deqing, Yang, Jun J., Khan, Raja B., Panetta, John C., Krull, Kevin R., Inaba, Hiroto, Rubnitz, Jeffrey E., Metzger, Monika L., Howard, Scott C., Ribeiro, Raul C., Cheng, Cheng, Reddick, Wilburn E., Jeha, Sima, Sandlund, John T., Evans, William E., Pui, Ching-Hon, Relling, Mary V.·2014·Journal of Clinical Oncology

DOI 10.1200/jco.2013.53.0808PMC PMC3948096

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Abstract

Purpose: Methotrexate (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 Methods: Prospective 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. Results: Fourteen 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. Conclusion: MTX-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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Pritchard, J. K., Stephens, M., & Donnelly, P. (2000) · Genetics · doi:10.1093/genetics/155.2.945 · Cited by 33,871
Classification and Regression Trees.
Gordon, A. D., Breiman, L., Friedman, J. H., Olshen, R. A., & Stone, C. J. (1984) · Biometrics · doi:10.2307/2530946 · Cited by 23,867
Classification and Regression Trees.
Ryzin, J. V., Breiman, L., Friedman, J. H., Olshen, R. A., & Stone, C. J. (1986) · Journal of the American Statistical Association · doi:10.2307/2288003 · Cited by 21,030
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
Glessner, J. T., Wang, K., Cai, G., Korvatska, O., Kim, C. E., Wood, S., Zhang, H., Estes, A., Brune, C. W., Bradfield, J. P., et al. (2009) · Nature · doi:10.1038/nature07953 · Cited by 1,421
Treating Childhood Acute Lymphoblastic Leukemia without Cranial Irradiation
Pui, C.-H., Campana, D., Pei, D., Bowman, W. P., Sandlund, J. T., Kaste, S. C., Ribeiro, R. C., Rubnitz, J. E., Raimondi, S. C., Onciu, M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900386 · Cited by 1,215
Self-citation
Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95
Möricke, A., Reiter, A., Zimmermann, M., Gadner, H., Stanulla, M., Dördelmann, M., Löning, L., Beier, R., Ludwig, W.-D., Ratei, R., et al. (2008) · Blood · doi:10.1182/blood-2007-09-112920 · Cited by 611
g:Profiler—a web server for functional interpretation of gene lists (2011 update)
Reimand, J., Arak, T., & Vilo, J. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr378 · Cited by 506
Rare Copy Number Variation Discovery and Cross-Disorder Comparisons Identify Risk Genes for ADHD
Lionel, A. C., Crosbie, J., Barbosa, N., Goodale, T., Thiruvahindrapuram, B., Rickaby, J., Gazzellone, M. J., Carson, A. R., Howe, J., Wang, Z., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002464 · Cited by 374
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Treviño, L. R., Shimasaki, N., Yang, W., Panetta, J. C., Cheng, C., Pei, D., Chan, D., Sparreboom, A., Giacomini, K. M., Pui, C., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.4156 · Cited by 353
Self-citation
Genome-wide association analysis identifies susceptibility loci for migraine without aura
Freilinger, T. M., Anttila, V., de Vries, B., Malik, R., Kallela, M., Terwindt, G. M., Pozo‐Rosich, P., Winsvold, B. S., Nyholt, D. R., van Oosterhout, W. P. J., et al. (2012) · Nature Genetics · doi:10.1038/ng.2307 · Cited by 350

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Show all 48 references

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Reddick WE, 2005, AJNR Am J Neuroradiol, 26, 2371

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Schilstra, C. E., McCleary, K., Fardell, J. E., Donoghoe, M. W., McCormack, E., Kotecha, R. S., Lourenco, R. D. A., Ramachandran, S., Cockcroft, R., Conyers, R. K., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21130091
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Authors: Bhojwani, D., Sabin, N. D., Pei, D., Yang, J. J., Khan, R. B., Panetta, J. C., Krull, K. R., Inaba, H., Rubnitz, J. E., Metzger, M. L., Howard, S. C., Ribeiro, R. C., Cheng, C., Reddick, W. E., Jeha, S., Sandlund, J. T., Evans, W. E., Pui, C.-H., & Relling, M. V.
Affiliations: St. Jude Children's Research Hospital (US)
ORCID: Bhojwani, Deepa
Sabin, Noah D.
Yang, Jun J.
Khan, Raja B.
Panetta, John C.
Krull, Kevin R.
Inaba, Hiroto
Rubnitz, Jeffrey E.
Metzger, Monika L.
Howard, Scott C.
Ribeiro, Raul C.
Cheng, Cheng
Reddick, Wilburn E.
Jeha, Sima
Evans, William E.
Pui, Ching-Hon
Relling, Mary V.
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2014-03-20
Volume: 32
Issue: 9
Pages: 949-959
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2013.53.0808
PMC: PMC3948096
OpenAlex: W2098676147
Cited by: 400
References: 48
Citations by year: 2026: 38 · 2025: 36 · 2024: 40 · 2023: 27 · 2022: 47 · 2021: 40 · 2020: 33 · 2019: 30 · 2018: 27 · 2017: 34 · 2016: 28 · 2015: 16 · 2014: 3
FWCI: 26.87
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA 36401, R01CA036401, R01 CA90246, R01CA090246, R37CA036401, P30CA021765)
National Institute of General Medical Sciences (U01GM092666, GM 92666)
Topics: Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords: methotrexate neurotoxicity, leukoencephalopathy, childhood acute lymphoblastic leukemia, intrathecal methotrexate, methotrexate pharmacokinetics, germline polymorphisms, neurodevelopmental genes, brain MRI
MeSH terms: Adolescent, Antimetabolites, Antineoplastic, Antineoplastic Combined Chemotherapy Protocols, Brain, Child, Child, Preschool, Leucovorin, Female, Humans, Magnetic Resonance Imaging, Male, Methotrexate, Polymorphism, Genetic, Prospective Studies, Risk Factors, Logistic Models, Germ-Line Mutation, Genetic Predisposition to Disease, Neurotoxicity Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Genome-Wide Association Study, Leukoencephalopathies

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Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia

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