ArticlePloS one2019
Changes in intracellular folate metabolism during high-dose methotrexate and Leucovorin rescue therapy in children with acute lymphoblastic leukemia.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- Toxicity-Tailored Thresholds of Delayed Methotrexate Elimination in Non-Hodgkin Lymphoma: A Population-Based Approach to Therapy Optimization.European journal of drug metabolism and pharmacokinetics · 2026Article
- Chemotherapy-induced oxidative injury in pediatric acute lymphoblastic leukemia: The role of N-acetylcysteine (Review).Biomedical reports · 2026Review
- Cerebral folate deficiency, developmental difficulties in autism spectrum disorder and the role of leucovorin: a narrative review of mechanisms and clinical evidence.Drugs in context · 2026Review
- Targeting the sulfur-containing amino acid pathway in leukemia.Amino acids · 2024Review
- Nutritional Approaches to Modulate Cardiovascular Disease Risk in Systemic Lupus Erythematosus: A Literature Review.Nutrients · 2023Review
- Selenofolate inhibits the proliferation of IGROV1 cancer cells independently from folate receptor alpha.Heliyon · 2021Article
- Corneal Epithelial Toxicity after Intravitreal Methotrexate Injection for Vitreoretinal Lymphoma: Clinical and In Vitro Studies.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethotrexate (MTX) is an important anti-folate agent in pediatric acute lymphoblastic leukemia (ALL) treatment. Folinic acid rescue therapy (Leucovorin) is administered after MTX to reduce toxicity. Previous studies hypothesized that Leucovorin could 'rescue' both normal healthy cells and leukemic blasts from cell death. We assessed whether Leucovorin is able to restore red blood cell folate levels after MTX.
methodsWe prospectively determined erythrocyte folate levels (5-methyltetrahydrofolate (THF) and non-methyl THF) and serum folate levels in 67 children with ALL before start (T0) and after stop (T1) of HD-MTX and Leucovorin courses.
resultsErythrocyte folate levels increased between T0 and T1 (mean ± SD: 416.7 ± 145.5 nmol/L and 641.2 ± 196.3 nmol/L respectively, p<0.001). This was due to an increase in 5-methyl THF levels (mean increase: 217.7 ± 209.5 nmol/L, p<0.001), whereas non-methyl THF levels did not change (median increase: 0.6 nmol/L [-9.9-11.1], p = 0.676). Serum folate levels increased between T0 and T1 (median increase: 29.2 nmol/L [32.9-74.0], p<0.001). Results were not significantly affected by age, sex, ALL immunophenotype and MTHFR c.677C>T genotype.
conclusionIntracellular folate levels accumulate after HD-MTX and Leucovorin therapy in children with ALL, suggesting that Leucovorin restores the intracellular folate pool. Future studies are necessary to assess concomitant lower uptake of MTX.
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