title: Use of allopurinol in children with acute lymphoblastic leukemia to reduce skewed thiopurine metabolism.
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.
authors.affiliation: Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
authors.forename: Julienne
authors.initials: J
authors.lastname: Brackett
authors.forename: Eric S
authors.initials: ES
authors.lastname: Schafer
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Leung
authors.forename: M Brooke
authors.initials: MB
authors.lastname: Bernhardt
mesh_terms: D000293:Adolescent; D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001711:Biotransformation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D060046:Maintenance Chemotherapy; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008727:Methotrexate / Q000008:administration & dosage; D008780:Methyltransferases / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D013873:Thionucleotides / Q000097:blood; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D000493:Allopurinol; C010240:6-methylthiopurine; D015122:Mercaptopurine; D014969:Xanthine Oxidase; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D008727:Methotrexate
keywords: acute lymphoblastic leukemia; allopurinol; hepatotoxicity; mercaptopurine; thiopurine metabolites