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Prolonged neutropenia after irinotecan-based chemotherapy in a child with polymorphisms of UGT1A1 and SLCO1B1

S Sakaguchi1, F Garcia-Bournissen, R Kim

  • 1Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. shinya.ito@sickkids.ca

Archives of Disease in Childhood
|July 18, 2009
PubMed

Insights

Genetic variations in UGT1A1 and SLCO1B1 increase irinotecan toxicity. This case report details combined UGT1A1 and SLCO1B1 polymorphisms in a child experiencing severe neutropenia, highlighting a potential risk factor in pediatric oncology.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Genetics

Background:

  • Genetic polymorphisms in uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) are established risk factors for irinotecan toxicity in adults.
  • Irinotecan is a crucial chemotherapy agent used in treating various pediatric cancers.
  • The combined impact of UGT1A1 and SLCO1B1 polymorphisms on irinotecan toxicity, particularly in pediatric populations, remains understudied.

Observation:

  • An 11-year-old female patient developed severe and prolonged neutropenia following irinotecan-based chemotherapy.
  • Genotyping revealed the presence of polymorphisms in both the UGT1A1 and SLCO1B1 genes in this patient.

Findings:

  • This case report presents the first documented instance of combined UGT1A1 and SLCO1B1 genotyping in a pediatric patient experiencing severe irinotecan-induced toxicity.
  • The co-occurrence of these genetic variations may significantly contribute to heightened susceptibility to severe adverse events like neutropenia in children undergoing irinotecan treatment.

Implications:

  • These findings suggest that combined UGT1A1 and SLCO1B1 genotyping could be a valuable tool for personalized irinotecan dosing and toxicity risk assessment in pediatric oncology.
  • Further research into the pharmacogenomic profiles of children treated with irinotecan is warranted to optimize treatment strategies and improve patient outcomes.
  • Identifying patients with combined UGT1A1 and SLCO1B1 polymorphisms could enable proactive management to mitigate severe neutropenia and other irinotecan-related toxicities.

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