Use of allopurinol in children with acute lymphoblastic leukemia to reduce skewed thiopurine metabolism

Pediatr Blood Cancer. 2014 Jun;61(6):1114-7. doi: 10.1002/pbc.24913. Epub 2013 Dec 27.

Abstract

Mercaptopurine (6-MP), a critical component of acute lymphoblastic leukemia (ALL) therapy, is metabolized to 6-thioguanine (6-TGN) which is responsible for its anti-leukemic effect, and to 6-methylmercaptopurine nucleotides (6-MMPN/6-MMP) which can be hepatotoxic. Some patients preferentially metabolize 6-MP to 6-MMPN which may increase the risk of liver injury, reduce serum levels of 6-TGN and potentially increase the risk of relapse. The addition of allopurinol to oral 6-MP has been shown to optimize metabolism towards 6-TGN in patients with inflammatory bowel disease (IBD); however, this use has not been reported in patients undergoing treatment for ALL.

Keywords: acute lymphoblastic leukemia; allopurinol; hepatotoxicity; mercaptopurine; thiopurine metabolites.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Allopurinol / pharmacology
  • Allopurinol / therapeutic use*
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biotransformation / drug effects
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Child, Preschool
  • Drug Evaluation
  • Female
  • Guanine Nucleotides / blood
  • Humans
  • Hyperbilirubinemia / chemically induced
  • Hypoxanthine Phosphoribosyltransferase / metabolism
  • Maintenance Chemotherapy
  • Male
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / adverse effects
  • Mercaptopurine / analogs & derivatives*
  • Mercaptopurine / blood
  • Mercaptopurine / pharmacokinetics*
  • Methotrexate / administration & dosage
  • Methyltransferases / metabolism
  • Neutropenia / chemically induced
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Thionucleotides / blood
  • Xanthine Oxidase / metabolism

Substances

  • Antimetabolites, Antineoplastic
  • Guanine Nucleotides
  • Thionucleotides
  • 6-thioguanylic acid
  • Allopurinol
  • 6-methylthiopurine
  • Mercaptopurine
  • Xanthine Oxidase
  • Methyltransferases
  • thiopurine methyltransferase
  • Hypoxanthine Phosphoribosyltransferase
  • Methotrexate