{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:06:14Z","timestamp":1761541574718,"version":"3.40.5"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up\u2010front window of Ma\u2010Spore ALL 2010 (MS2010) study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We randomised 429 children with newly diagnosed ALL to 15\u2010minute <jats:italic>vs<\/jats:italic> 3\u2010hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B\u2010ALL and 20 T\u2010ALL patients, we performed VCR plasma (<jats:italic>n<\/jats:italic> = 135 patients) and intracellular (<jats:italic>n<\/jats:italic> = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and <jats:italic>ABCB1<\/jats:italic> genotypes were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was no significant difference between 15\u2010minute and 3\u2010hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B\u2010ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR<jats:sub>24h<\/jats:sub> levels (<jats:italic>P<\/jats:italic> = .03 and <jats:italic>P<\/jats:italic> = .04, respectively). The median VCR<jats:sub>24h<\/jats:sub> intracellular levels were similar among the common genetic subtypes of ALL (<jats:italic>P<\/jats:italic> = .4). Patients homozygous for wild\u2010type <jats:italic>ABCB1<\/jats:italic> 2677GG had significantly higher median intracellular VCR<jats:sub>24h<\/jats:sub> (<jats:italic>P<\/jats:italic> = .04) than 2677TT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We showed that in childhood B\u2010ALL, the intracellular VCR<jats:sub>24h<\/jats:sub> levels in lymphoblasts affected treatment outcomes. The intracellular VCR<jats:sub>24h<\/jats:sub> level was independent of leukaemia subtype but dependent on host <jats:italic>ABCB1<\/jats:italic> G2677T genotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14596","type":"journal-article","created":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T08:01:34Z","timestamp":1602316894000},"page":"1990-1999","source":"Crossref","is-referenced-by-count":2,"title":["Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B\u2010lymphoblastic leukaemia: Ma\u2010Spore ALL 2010 study"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7661-5728","authenticated-orcid":false,"given":"Nan","family":"Jiang","sequence":"first","affiliation":[{"name":"VIVA\u2010NUS Centre for Translational Research in Acute Leukaemia, Department of Paediatrics, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqiang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmacy Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Li","sequence":"additional","affiliation":[{"name":"VIVA\u2010NUS Centre for Translational Research in Acute Leukaemia, Department of Paediatrics, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwynn Kean Hui","family":"Chiew","sequence":"additional","affiliation":[{"name":"VIVA\u2010NUS Centre for Translational Research in Acute Leukaemia, Department of Paediatrics, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yok Moi","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"How Sung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai Peng","family":"Lin","sequence":"additional","affiliation":[{"name":"Sime Darby Medical Centre  Subang Jaya Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ah Moy","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics KK Women's &amp; Cheildren's Hospital  Singapore 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