Thiopurine S-methyltransferase gene polymorphism and 6-mercaptopurine dose intensity in Indian children with acute lymphoblastic leukemia

Leuk Res. 2010 Aug;34(8):1023-6. doi: 10.1016/j.leukres.2010.01.029. Epub 2010 Feb 13.

Abstract

The prevalence of thiopurine S-methyltransferase (TPMT) polymorphism and its association with clinical and hematological toxicities was retrospectively analyzed in 71 Indian children with acute lymphoblastic leukemia (ALL). Only heterozygous TPMT alleles were observed (10%, 7/71) with relative frequencies being *1/*3C (4.2%), *1/*2 (4.2%) and *1/*3A (1.4%). The median 6-mercaptopurine dose administered during the maintenance therapy was 31% lower among patients with heterozygous TPMT alleles versus the rest (32.1mg/m(2)/day and 46.2mg/m(2)/day, p=0.005), though the myelosuppression and toxicities were similar in both the groups. Identification of TPMT genotype appears to be important in making the ALL treatment more effective and less toxic.

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Humans
  • India
  • Infant
  • Male
  • Mercaptopurine / administration & dosage*
  • Methyltransferases / genetics*
  • Polymorphism, Genetic / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Mercaptopurine
  • Methyltransferases
  • thiopurine methyltransferase