دورية أكاديمية
Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia.
| العنوان: | Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia. |
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| المؤلفون: | Mahmoud LB; Department of Pharmacology, Faculty of Medicine, University of Sfax, Tunisia., Mdhaffar M; Department of Hematology, Hedi Chaker University Hospital, Sfax, Tunisia., Frikha R; Department of Histology, Faculty of Medicine, University of Sfax, Tunisia., Ghozzi H; Department of Pharmacology, Faculty of Medicine, University of Sfax, Tunisia., Hakim A; Department of Pharmacology, Faculty of Medicine, University of Sfax, Tunisia., Sahnoun Z; Department of Pharmacology, Faculty of Medicine, University of Sfax, Tunisia., Elloumi M; Department of Hematology, Hedi Chaker University Hospital, Sfax, Tunisia., Zeghal K; Department of Pharmacology, Faculty of Medicine, University of Sfax, Tunisia. |
| المصدر: | Advances in clinical and experimental medicine : official organ Wroclaw Medical University [Adv Clin Exp Med] 2018 Aug; Vol. 27 (8), pp. 1061-1068. |
| نوع المنشور: | Clinical Trial; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The University Country of Publication: Poland NLM ID: 101138582 Publication Model: Print Cited Medium: Print ISSN: 1899-5276 (Print) Linking ISSN: 18995276 NLM ISO Abbreviation: Adv Clin Exp Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Wroclaw, Poland : The University, |
| مواضيع طبية MeSH: | Antimetabolites, Antineoplastic/*adverse effects , Methotrexate/*adverse effects , Methylenetetrahydrofolate Reductase (NADPH2)/*genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics, Adolescent ; Adult ; Antimetabolites, Antineoplastic/blood ; Antimetabolites, Antineoplastic/pharmacokinetics ; Child ; Child, Preschool ; Female ; Genotype ; Humans ; Infant ; Male ; Methotrexate/blood ; Methotrexate/pharmacokinetics ; Polymorphism, Single Nucleotide/genetics ; Young Adult |
| مستخلص: | 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 Treatment of Cancer - Children's Leukemia Group (EORTC-CLG) protocol, were prospectively enrolled. Toxicity data was collected objectively after each high-dose methotrexate (HD-MTX) course. The risk factors of MTX toxicity were determined using multiple linear regression analysis, with age, gender, immunophenotype, risk group, plasma MTX levels, plasma homocysteine (HCY) levels, and MTHFR C677T included as independent variables. Results: Twenty-five (71.4%) patients experienced toxicity on at least 1 course of HD-MTX. In the univariate linear regression, the global toxicity score was associated with a significant rise in plasma HCY concentrations within 48 h after MTX administration (β = 0.4; R2 = 0.12; p = 0.02). In the multiple regression model, the global toxicity score was significantly associated with a higher MTX plasma levels at 48 h (β = 0.5; R2 = 0.38; p = 0.001) and CT 677 MTHFR genotype (β = 0.3; R2 = 0.38; p = 0.01). Conclusions: Routine monitoring of plasma MTX concentrations is essential to detect patients at a high risk of MTX toxicity. MTHFR C677T genotyping may be useful for predicting MTX toxicity. |
| فهرسة مساهمة: | Keywords: MTHFR C677T polymorphism; acute lymphoblastic leukemia; methotrexate; toxicity |
| المشرفين على المادة: | 0 (Antimetabolites, Antineoplastic) EC 1.5.1.20 (MTHFR protein, human) EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2)) YL5FZ2Y5U1 (Methotrexate) |
| تواريخ الأحداث: | Date Created: 20180619 Date Completed: 20181212 Latest Revision: 20220409 |
| رمز التحديث: | 20221213 |
| DOI: | 10.17219/acem/69802 |
| PMID: | 29911750 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1899-5276 |
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| DOI: | 10.17219/acem/69802 |