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Prolonged Neutropenia after Irinotecan-based Chemotherapy in a Child with polymorphisms of UGT1A1 and SLCO1B1
  1. Sachi Sakaguchi (sachi.sakaguchi{at}sickkids.ca)
  1. Division of Clinical Pharmacology, Hospital for Sick Children, Canada
    1. Facundo Garcia-Bournissen (facugb{at}hotmail.com)
    1. Division of Clinical Pharmacology, Hospital for Sick Children, Canada
      1. Richard Kim (richard.kim{at}lhsc.on.ca)
      1. Division of Clinical Pharmacology, The University of Western Ontario, Canada
        1. Ute Schwarz (ute.schwarz{at}sickkids.ca)
        1. Division of Clinical Pharmacology, The University of Western Ontario, Canada
          1. Paul C Nathan (paul.nathan{at}sickkids.ca)
          1. Division of Haematology and Oncology, Hospital for Sick Children, Canada
            1. Shinya Ito (shinya.ito{at}sickkids.ca)
            1. Division of Clinical Pharmacology, Hospital for Sick Children, Canada

              Abstract

              Genetic polymorphisms of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and SLCO1B1 coding organic anion-transporter polypeptide 1B1 are independent risk factors known to increase irinotecan toxicity in adults. Although combined occurrence of polymorphisms in these 2 genes is likely to influence susceptibility to irinotecan toxicity, data are scarce, especially in children. We report an 11 year old female with severe and prolonged neutropenia after irinotecan-based chemotherapy. The patient’s genotyping revealed polymorphisms in both UGT1A1 and SLCO1B1. To our knowledge, this is the first case report of combined genotyping of both UGT1A1 and SLCO1B1 in a child with severe irinotecan toxicity.

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