{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:39:07Z","timestamp":1792795147143,"version":"4.5.0"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:00:00Z","timestamp":1689379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:00:00Z","timestamp":1689379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["CTRQQR-2021\\100003"],"award-info":[{"award-number":["CTRQQR-2021\\100003"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Experimental Cancer Medicine Centre Network","award":["ECMCQQR-2022\/100002"],"award-info":[{"award-number":["ECMCQQR-2022\/100002"]}]},{"DOI":"10.13039\/501100022850","name":"Little Princess Trust","doi-asserted-by":"publisher","award":["CCLGA 2021 08 Veal"],"award-info":[{"award-number":["CCLGA 2021 08 Veal"]}],"id":[{"id":"10.13039\/501100022850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Dubin\u2013Johnson syndrome is a rare benign autosomal recessive condition that causes an isolated increase of conjugated bilirubin in the serum. Impaired biliary excretion is due to mutation in the multiple drug-resistance protein 2 gene (MRP2).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We describe the case of a 4-year-old girl being treated for acute lymphoblastic leukaemia who had a history of conjugated hyperbilirubinaemia and persistently elevated bilirubin levels on initiation of chemotherapy. During treatment for leukaemia, she was diagnosed with Dubin\u2013Johnson syndrome for the underlying condition. Following administration of vincristine at the recommended dose of 1.5\u00a0mg\/m<jats:sup>2<\/jats:sup>, an abnormally high vincristine exposure was observed (AUC\u2009&gt;\u2009200\u00a0\u00b5g\/L*h), approximately 3 times higher than previously reported exposures in a comparable clinical setting. Vincristine dose reductions were applied on subsequent cycles of treatment and resulted in markedly reduced drug exposures, within the normal target range.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This case provided a rare opportunity to assess the impact of MRP2 mutations associated with Dubin\u2013Johnson syndrome on the pharmacokinetics of vincristine and strongly indicates that a marked dose reduction should be recommended. Clinicians should be made aware of the potential for altered drug disposition for agents such as vincristine in patients with this rare genetic condition.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00280-023-04565-0","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T09:02:11Z","timestamp":1689411731000},"page":"325-328","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Excessive vincristine exposure in a child being treated for acute lymphoblastic leukaemia with underlying Dubin\u2013Johnson syndrome: a case report"],"prefix":"10.1007","volume":"92","author":[{"given":"Shelby","family":"Barnett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aye Chan","family":"Nyein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Galler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jamieson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-8678","authenticated-orcid":false,"given":"Gareth J.","family":"Veal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,15]]},"reference":[{"issue":"1","key":"4565_CR1","doi-asserted-by":"publisher","first-page":"6756","DOI":"10.1038\/s41598-020-63528-0","volume":"10","author":"A Kakaje","year":"2020","unstructured":"Kakaje A et al (2020) Rates and trends of childhood acute lymphoblastic leukaemia: an epidemiology study. Sci Rep 10(1):6756","journal-title":"Sci Rep"},{"issue":"11","key":"4565_CR2","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.3324\/haematol.2020.247031","volume":"105","author":"H Inaba","year":"2020","unstructured":"Inaba H, Mullighan CG (2020) Pediatric acute lymphoblastic leukemia. Haematologica 105(11):2524\u20132539","journal-title":"Haematologica"},{"issue":"3","key":"4565_CR3","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S1040-8428(98)00023-7","volume":"29","author":"CE Gidding","year":"1999","unstructured":"Gidding CE et al (1999) Vincristine revisited. 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