Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia.

@article{Mahmoud2018UseOM,
  title={Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia.},
  author={Lobna Ben Mahmoud and Moez Mdhaffar and Rim Frikha and Hanen Ghozzi and Ahmed Hakim and Zouheir Sahnoun and Moez Elloumi and Khaled Mounir Zeghal},
  journal={Advances in clinical and experimental medicine : official organ Wroclaw Medical University},
  year={2018},
  volume={27 8},
  pages={
          1061-1068
        }
}
  • L. Mahmoud, M. Mdhaffar, +5 authors K. Zeghal
  • Published 1 August 2018
  • Medicine
  • Advances in clinical and experimental medicine : official organ Wroclaw Medical University
BACKGROUND Methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy, but it is associated with serious toxicities in a considerable number of patients. OBJECTIVES The aim of the current study was to determine which variables were associated with MTX toxicity in children, adolescents and young adults with ALL. MATERIAL AND METHODS In this prospective study, 35 patients with newly diagnosed ALL, treated according to the 58951 European Organization for Research and… Expand
The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
TLDR
Neither MTHFR C677T nor A1298C polymorphisms were significantly associated with delayed MTX clearance, and were not good predictors of MTX-related toxicities. Expand
Identifying risk factors for high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia
TLDR
Routine monitoring of 44-h MTX concentrations is essential to identify patients at high risk of developing febrile neutropenia and vomiting and may provide a reference for clinicians to distinguish patients with a relatively highrisk of severe AEs based on certain characteristics before HD-MTX infusion. Expand
Comprehensive analysis of Methylenetetrahydrofolate reductase C677T in younger acute lymphoblastic leukemia patients: A single-center experience
  • R. Frikha, T. Rebai, +5 authors N. Bouayed
  • Medicine
  • Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
  • 2019
TLDR
The findings suggest that C677T polymorphism of MTHFR seems to be a good marker for MTX-related toxicity in ALL. Expand
A prospective study of a simple algorithm to individually dose high-dose methotrexate for children with leukemia at risk for methotrexate toxicities
TLDR
A simple algorithm to individualize HDMTX infusions with 0–2 rate adjustments based on methotrexate levels during the infusion is developed and is a simple, safe and effective method for individualizing HD MTX in pediatric patients with ALL. Expand
Serum Methotrexate Level and Side Effects of High Dose Methotrexate Infusion in Pediatric Patients with Acute Lymphoblastic Leukaemia (ALL)
TLDR
Dose reduction, increased the length of stay and treatment delay occurred in patients with severe toxicities, which can be interrelated with serum methotrexate levels at 48 h after the start of HDMTX infusion. Expand
Clinical Implications of Methotrexate Pharmacogenetics in Childhood Acute Lymphoblastic Leukaemia.
TLDR
Why, in spite of the significant research efforts, pharmacogenetics findings in this setting have not yet found their way into routine clinical practice is described. Expand
Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia
TLDR
The findings showed that genetic polymorphism could be associated with plasma MTX levels, toxicity experienced and EFS in Iranian pediatric ALL. Expand
Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies
TLDR
A systematic review of germline pharmacogenetic association studies of genetic associations influencing high-dose methotrexate elimination in children with cancer concludes that there is only one gene that reliably demonstrates an effect on MTX pharmacokinetics: SLCO1B1. Expand
Genetic variants associated with methotrexate-induced mucositis in cancer treatment: a systematic review and meta-analysis.
TLDR
Previously studied genetic variants in relation to MTX-induced mucositis are reviewed and meta-analyze for single nucleotide polymorphisms (SNPs) for which at least two studies found a statistically significant association. Expand
Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology
TLDR
An overview of new developments over the past four years regarding relevant polymorphisms related to toxicity in pediatric oncology and several questions regarding the role of genetic variants in chemotherapy-induced toxicities are identified. Expand
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The pharmacogenetics of methotrexate (MTX) was investigated in a large cohort of pediatric patients with acute lymphoblastic leukemia and genetic variations substantially influence the kinetics and response to high-dose MTX therapy in childhood ALL. Expand
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There was a statistically significant increase in the risk of non‐Hodgkin lymphoma in patients with CT genotype in patients treated with methotrexate maintenance therapy, and MTHFR 677C>T polymorphism (CT + TT) was significantly overrepresented among cases with hepatic toxicity. Expand
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