{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:04:28Z","timestamp":1753869868322,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP160771","RP230026"],"award-info":[{"award-number":["RP160771","RP230026"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Delayed excretion of high\u2010dose methotrexate (HD\u2010MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD\u2010MTX 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\u2010MTX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multisite chart review included pediatric patients with ALL (2010\u20132020) who received HD\u2010MTX (5\u00a0g\/m<jats:sup>2<\/jats:sup>). Delayed excretion was defined as a serum MTX concentration greater than 0.4\u00a0\u00b5M at Hour 48. We identified use of laxative medications after each HD\u2010MTX 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\u2010MTX excretion to account for multiple MTX cycles per individual.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 533 eligible patients received 1875 HD\u2010MTX infusions. Patients were mostly male (59.8%), Hispanic (56.7%), with a median age of 9.5\u00a0years. Delayed excretion was observed following 42.7% of HD\u2010MTX 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\u20132.09; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.002) more likely to experience delayed excretion compared to those receiving fewer than two laxative doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31377","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T13:11:10Z","timestamp":1728565870000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delayed excretion of high\u2010dose methotrexate in pediatric acute leukemia correlates with laxative and constipation management"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-0395","authenticated-orcid":false,"given":"Jennifer A.","family":"Belsky","sequence":"first","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7986-601X","authenticated-orcid":false,"given":"Ashley","family":"Chavana","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankona","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-906X","authenticated-orcid":false,"given":"Mark","family":"Zobeck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Cancer and Hematology Center Texas Children's Hospital  Houston Texas 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Brooke","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Science St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"SEER Preliminary Cancer Incidence Rate Estimates for 2017 and diagnosis years 2000 to 2017 SEER 18 National Cancer Institute. Bethesda MD https:\/\/seer.cancer.gov\/statistics\/preliminary\u2010estimates\/ based on the February 2019 SEER data submission and the November 2018 SEER data submission. 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