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Excessive vincristine exposure in a child being treated for acute lymphoblastic leukaemia with underlying Dubin–Johnson syndrome: a case report

Lookup NU author(s): Dr Shelby BarnettORCiD, Dr Martin Galler, Dr David Jamieson, Professor Gareth Veal



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023, The Author(s).Background: Dubin–Johnson 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). Case presentation: 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–Johnson syndrome for the underlying condition. Following administration of vincristine at the recommended dose of 1.5 mg/m2, an abnormally high vincristine exposure was observed (AUC > 200 µg/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. Conclusion: This case provided a rare opportunity to assess the impact of MRP2 mutations associated with Dubin–Johnson 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.

Publication metadata

Author(s): Barnett S, Nyein AC, Galler M, Jamieson D, Davies M, Connor P, Veal GJ

Publication type: Article

Publication status: Published

Journal: Cancer Chemotherapy and Pharmacology

Year: 2023

Volume: 92

Pages: 325–328

Online publication date: 15/07/2023

Acceptance date: 01/07/2023

Date deposited: 08/08/2023

ISSN (print): 0344-5704

ISSN (electronic): 1432-0843

Publisher: Springer Science and Business Media Deutschland GmbH


DOI: 10.1007/s00280-023-04565-0

PubMed id: 37452859


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Funder referenceFunder name
Cancer Research UK
CCLGA 2021 08
Experimental Cancer Medicine Centre Network
Little Princess Trust