Association of ITPA genotype with event-free survival and relapse rates in children with acute lymphoblastic leukemia undergoing maintenance therapy

PLoS One. 2014 Oct 10;9(10):e109551. doi: 10.1371/journal.pone.0109551. eCollection 2014.

Abstract

Although the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, failure due to treatment-related toxicities and relapse of the disease still occur in about 20% of patients. This retrospective study included 308 pediatric ALL patients undergoing maintenance therapy and investigated the effects of genetic variants of enzymes involved in the 6-mercaptopurine (6-MP) metabolism and folate pathway on survival and relapse rates. The presence of at least one of the non-functional ITPA alleles (94C>A and/or IVS2+21A>C variant) was associated with longer event-free survival compared to patients with the wild-type ITPA genotype (p = 0.033). Furthermore, patients carrying at least one non-functional ITPA allele were shown to be at a lower risk of suffering early (p = 0.003) and/or bone marrow relapse (p = 0.017). In conclusion, the ITPA genotype may serve as a genetic marker for the improvement of risk stratification and therapy individualization for patients with ALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Antineoplastic Agents / therapeutic use
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Gene Frequency
  • Genotype*
  • Humans
  • Infant
  • Male
  • Neoplasm Recurrence, Local / genetics*
  • Polymorphism, Single Nucleotide*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Pyrophosphatases / genetics*
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Pyrophosphatases
  • ITPA protein, human

Grants and funding

This work was supported by Slovenian Research Agency grant No. J3-3615. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.