Delayed excretion of high-dose methotrexate in pediatric acute leukemia correlates with laxative and constipation management.

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  • Additional Information
    • Source:
      Publisher: John Wiley Country of Publication: United States NLM ID: 101186624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-5017 (Electronic) Linking ISSN: 15455009 NLM ISO Abbreviation: Pediatr Blood Cancer Subsets: MEDLINE
    • Publication Information:
      Original Publication: Hoboken, N.J. : John Wiley, c 2004-
    • Subject Terms:
      Methotrexate*/administration & dosage ; Methotrexate*/pharmacokinetics ; Methotrexate*/adverse effects ; Constipation*/chemically induced ; Constipation*/drug therapy ; Laxatives*/administration & dosage ; Precursor Cell Lymphoblastic Leukemia-Lymphoma*/drug therapy ; Antimetabolites, Antineoplastic*/administration & dosage ; Antimetabolites, Antineoplastic*/adverse effects ; Antimetabolites, Antineoplastic*/pharmacokinetics; Humans ; Male ; Female ; Child ; Child, Preschool ; Adolescent ; Retrospective Studies ; Follow-Up Studies ; Prognosis ; Infant
    • Abstract:
      Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.
      Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m 2 ). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered a proxy for constipation. Multilevel logistic regression models evaluated associations between clinical factors and delayed HD-MTX excretion to account for multiple MTX cycles per individual.
      Results: A total of 533 eligible patients received 1875 HD-MTX infusions. Patients were mostly male (59.8%), Hispanic (56.7%), with a median age of 9.5 years. Delayed excretion was observed following 42.7% of HD-MTX infusions, and patients received two or more laxative doses during 19.9% of infusions. Independent of other factors, individuals who received two or more laxative doses were nearly 60% (odds ratio 1.58; 95% confidence interval: 1.19-2.09; p = .002) more likely to experience delayed excretion compared to those receiving fewer than two laxative doses.
      Conclusion: Receipt of at least two laxative doses was independently associated with delayed methotrexate excretion in pediatric patients with ALL. Future prospective studies are needed to confirm the secondary effects of constipation and confirm the association with constipation and identify clinical benefits that optimize drug excretion.
      (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
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    • Grant Information:
      R01CA272981 National Institutes of Health National Cancer Institute; P20CA262733 National Institutes of Health National Cancer Institute; K12CA090433 National Institutes of Health National Cancer Institute; RP160771 Cancer Prevention & Research Institute of Texas; RP230026 Cancer Prevention & Research Institute of Texas; St. Baldrick's Foundation Consortium Research Grant; Indiana University Simon Comprehensive Cancer Center Pilot Funding; Team Joey Foundation
    • Contributed Indexing:
      Keywords: ALL; Chemotherapy; Methotrexate
    • Accession Number:
      YL5FZ2Y5U1 (Methotrexate)
      0 (Laxatives)
      0 (Antimetabolites, Antineoplastic)
    • Publication Date:
      Date Created: 20241010 Date Completed: 20241122 Latest Revision: 20241203
    • Publication Date:
      20241204
    • Accession Number:
      10.1002/pbc.31377
    • Accession Number:
      39387373