{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T13:05:56Z","timestamp":1779541556679,"version":"3.53.1"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The pro\u2010drug 6\u2010mercaptopurine (6\u2010MP), essential during maintenance, is converted into active 6\u2010thioguanine (6\u2010TGN) and toxic 6\u2010methylmercaptopurine (6\u2010MMP) metabolites, resulting in marked variability in efficacy and toxicity. 6\u2010MP therapy is further limited by poor adherence, variable absorption, and complex metabolism. Allopurinol is sometimes used to correct skewed metabolism, though its precise clinical role remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study aimed to develop population pharmacokinetic (popPK)\u2010based strategies to optimize 6\u2010MP dosing in children and improve therapeutic outcomes. A popPK model was developed using 6\u2010MMP and 6\u2010TGN concentrations from the pediatric oncology cohort. Model\u2010based simulations in 1000 virtual patients were performed to explore optimized dosing strategies, with and without allopurinol, aiming to reach the therapeutic target (6\u2010MMP &lt;5700\u00a0pmol\/8\u00a0\u00d7\u00a010\n                      <jats:sup>8<\/jats:sup>\n                      \u00a0RBC and 6\u2010TGN between 230 and 450\u00a0pmol\/8\u00a0\u00d7\u00a010\n                      <jats:sup>8<\/jats:sup>\n                      \u00a0RBC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The popPK model revealed a linear correlation between 6\u2010MP dose and metabolite concentrations. Allopurinol co\u2010administration substantially shifted metabolites\u2019 distribution from 80% 6\u2010MMP\/20% 6\u2010TGN to 21% 6\u2010MMP\/79% 6\u2010TGN. Simulations identified optimal 6\u2010MP doses of 40\u201375\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      without allopurinol, and only 10\u201315\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      when co\u2010administered.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Allopurinol co\u2010treatment reduces toxicity while maintaining therapeutic efficacy at lower 6\u2010MP doses. The proposed model warrants prospective evaluation for clinical relevance confirmation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70167","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:27:11Z","timestamp":1772980031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Model\u2010Based Strategy for 6\u2010Mercaptopurine Treatment in Acute Lymphoblastic Leukemia Maintenance Phase: Prediction of 6\u2010TGN and 6\u2010MMP Concentrations to Optimize Treatment"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5795-9394","authenticated-orcid":false,"given":"Anne","family":"Ravix","sequence":"first","affiliation":[{"name":"Centre for Research and Innovation in Clinical Pharmaceutical Sciences Lausanne University Hospital and University of Lausanne  Lausanne 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