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: Julienne Brackett, Eric S Schafer, Daniel H Leung, M Brooke Bernhardt
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 61 Issue 6 Pg. 1114-7 (Jun 2014) ISSN: 1545-5017 [Electronic] United States
• PMID: 24376133 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

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

Topics

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