{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:44:51Z","timestamp":1788443091988,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022QH027"],"award-info":[{"award-number":["ZR2022QH027"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018546","name":"Postdoctoral Innovation Project of Shandong Province","doi-asserted-by":"publisher","award":["SDCX\u2010ZG\u2010202203038"],"award-info":[{"award-number":["SDCX\u2010ZG\u2010202203038"]}],"id":[{"id":"10.13039\/501100018546","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>Continuous 6\u2010mercaptopurine (6\u2010MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose\u2010limiting hematopoietic toxicity. However, evidence\u2010based guidelines for gene\u2010based 6\u2010MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open\u2010label, active\u2010controlled clinical trial randomly assigned Chinese children with low\u2010 or intermediate\u2010risk ALL in a 1:1 ratio to receive <jats:italic>TPMT<\/jats:italic>\u2013<jats:italic>NUDT15<\/jats:italic> gene\u2013based dosing of 6\u2010MP (<jats:italic>N<\/jats:italic>\u2009=\u200944, 10 to 50\u2009mg\/m<jats:sup>2<\/jats:sup>\/day) or standard dosing (<jats:italic>N<\/jats:italic>\u2009=\u200944, 50\u2009mg\/m<jats:sup>2<\/jats:sup>\/day) during maintenance therapy. The primary end point was the incidence of 6\u2010MP myelosuppression in both groups. Secondary end points included frequencies of 6\u2010MP hepatotoxicity, duration of myelosuppression and leukopenia, event\u2010free survival, and steady\u2010state concentrations of active metabolites (6\u2010thioguaninenucleotides and 6\u2010methylmercaptopurine nucleotides) in erythrocytes. A 2.2\u2010fold decrease in myelosuppression, the primary end point, was observed in the gene\u2010based\u2013dose group using ~\u200950% of the standard initial 6\u2010MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, <jats:italic>P<\/jats:italic>\u2009=\u20090.003). Patients in the gene\u2010based\u2013dose group had a significantly lower risk of developing thiopurine\u2010induced myelosuppression and leukopenia (<jats:italic>P<\/jats:italic>\u2009=\u20090.015 and <jats:italic>P<\/jats:italic>\u2009=\u20090.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady\u2010state concentrations of active metabolites in erythrocytes between the two groups. <jats:italic>TPMT\u2010<\/jats:italic> and <jats:italic>NUDT15<\/jats:italic>\u2010based dosing of 6\u2010MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinicaltrial.gov\">www.clinicaltrial.gov<\/jats:ext-link> as #NCT04228393.<\/jats:p>","DOI":"10.1002\/cpt.3061","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T10:38:25Z","timestamp":1695811105000},"page":"213-220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Individualized Use of 6\u2010Mercaptopurine in Chinese Children with <scp>ALL<\/scp>: A Multicenter Randomized Controlled Trial"],"prefix":"10.1002","volume":"115","author":[{"given":"Yue","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Oncology Children's Hospital of Hebei Province affiliated to Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Rong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hematology Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem Institute of Hematology &amp; Blood Diseases Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Shandong, First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi\u2010Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"},{"name":"Department of Pharmacy China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Li","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Oncology Children's Hospital of Hebei Province affiliated to Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei\u2010Bei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem Institute of Hematology &amp; Blood Diseases Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Qiu","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Song","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd.  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd.  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hematology Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Juan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hematology Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Shandong, First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"van den Anker","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Children's National Medical Center  Washington DC USA"},{"name":"Departments of Pediatrics, Pharmacology &amp; 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