Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol

R. Franca, P. Rebora, N. Bertorello, F. Fagioli, V. Conter, A. Biondi, A. Colombini, C. Micalizzi, M. Zecca, R. Parasole, F. Petruzziello, G. Basso, M. C. Putti, F. Locatelli, P. d'Adamo, M. G. Valsecchi, G. Decorti, M. Rabusin

Research output: Contribution to journalArticle

Abstract

Drug-related toxicities represent an important clinical concern in chemotherapy, genetic variants could help tailoring treatment to patient. A pharmacogenetic multicentric study was performed on 508 pediatric acute lymphoblastic leukemia patients treated with AIEOP-BFM 2000 protocol: 28 variants were genotyped by VeraCode and Taqman technologies, deletions of GST-M1 and GST-T1 by multiplex PCR. Toxicities were derived from a central database: 251 patients (49.4%) experienced at least one gastrointestinal (GI) or hepatic (HEP) or neurological (NEU) grade III/IV episode during the remission induction phase: GI occurred in 63 patients (12.4%); HEP in 204 (40.2%) and NEU in 44 (8.7%). Logistic regression model adjusted for sex, risk and treatment phase revealed that ITPA rs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1 rs246240 and ADORA2A rs2236624 homozygous mutated genotypes were associated to NEU and HEP, respectively. These three variants could be putative predictive markers for chemotherapy-related toxicities in AIEOP-BFM protocols.
Original languageEnglish
Pages (from-to)4-10
Number of pages7
JournalPharmacogenomics Journal
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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Keywords

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects/pharmacokinetics
  • Chemical and Drug Induced Liver Injury/etiology/genetics
  • Child
  • Child, Preschool
  • Clinical Trials as Topic
  • Consolidation Chemotherapy/adverse effects
  • Female
  • Gastrointestinal Diseases/chemically induced/genetics
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Glutathione Transferase/genetics
  • Humans
  • Induction Chemotherapy/adverse effects
  • Infant
  • Logistic Models
  • Male
  • Multidrug Resistance-Associated Proteins/genetics
  • Multiplex Polymerase Chain Reaction
  • Mutation
  • Nervous System Diseases/chemically induced/genetics
  • Pharmacogenetics/methods
  • Pharmacogenomic Testing/methods
  • Pharmacogenomic Variants
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/metabolism/pathology
  • Predictive Value of Tests
  • Pyrophosphatases/genetics
  • Receptor, Adenosine A2A/genetics
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome

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