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

• DOI: 10.1007/s00280-023-04565-0
• Publication Date: 2023-07-15T09:02:11Z
• Authors: Shelby Barnett; Aye Chan Nyein; Martin Galler; David Jamieson; Michelle Davies; Philip Connor; Gareth J. Veal
• Keywords: Jaundice, Chronic Idiopathic; Vincristine; Short Communication; Child, Preschool; Humans; Female; Bilirubin; Multidrug Resistance-Associated Proteins; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Child; Multidrug Resistance-Associated Protein 2; 3. Good health

Dubin-Johnson syndrome is a rare benign autosomal recessive condition that causes an isolated increase of conjugated bilirubin in the serum. Impaired biliary excretion due to mutation multiple drug-resistance protein 2 gene (MRP2).We describe case 4-year-old girl being treated for acute lymphoblastic leukaemia who had history hyperbilirubinaemia and persistently elevated levels on initiation chemotherapy. During treatment leukaemia, she was diagnosed with underlying condition. Following administration vincristine at recommended dose 1.5 mg/m2, abnormally high exposure observed (AUC > 200 µg/L*h), approximately 3 times higher than previously reported exposures comparable clinical setting. Vincristine reductions were applied subsequent cycles resulted markedly reduced drug exposures, within normal target range.This provided opportunity assess impact MRP2 mutations associated pharmacokinetics strongly indicates marked reduction should be recommended. Clinicians made aware potential altered disposition agents such as patients this genetic