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Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine

Leukemia volume 16, pages 209–212 (2002)Cite this article

Abstract

Methotrexate is widely administered with mercaptopurine, a prodrug requiring activation into thioguanine nucleotides (TGN) to exert antileukemic effects. In vitro, methotrexate enhances TGN formation, but in vivo, such enhancement has yet to be demonstrated. We investigated whether TGN concentrations were related to methotrexate concentrations in children with acute lymphoblastic leukemia who received a weekly intravenous methotrexate (40 mg/m2) dose combined with daily mercaptopurine (75 mg/m2). A total of 141 erythrocyte TGN concentrations were measured with erythrocyte methotrexate polyglutamates (MTX-PG) concentrations in 87 patients. Average TGN concentrations ranged from 137 to 958 pmol/8 × 108 cells (median 389), average total MTX-PG concentrations (MTX- PG1–7) from 0.60 to 97.7 pmol/109cells (median 29), and average long chain polyglutamate concentrations (MTX-PG5–7) from 0 to 8.35 pmol/109 cells (median 2.43). Higher TGN concentrations correlated with higher MTX-PG5–7 concentrations (P = 0.002). These data support the practice of administering methotrexate with mercaptopurine during continuation therapy of acute lymphoblastic leukemia.

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Acknowledgements

This work was supported by grants CA 36401, CA 78224 and CA21765 from the National Institutes of Health; by a Center of Excellence grant from the State of Tennessee; and by American Lebanese Syrian Associated Charities (ALSAC).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA

    T Dervieux, W Evans & MV Relling

  2. Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN, USA

    M Hancock

  3. Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA

    C-H Pui

  4. University of Tennessee, Memphis, TN, USA

    W Evans, C-H Pui & MV Relling

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  1. T Dervieux
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  2. M Hancock
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Dervieux, T., Hancock, M., Evans, W. et al. Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine. Leukemia 16, 209–212 (2002). https://doi.org/10.1038/sj.leu.2402373

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