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

Author

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

Published
2015
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3. Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol

Author

Francesco Locatelli, Pio D'Adamo, Marco Zecca, Maria Grazia Valsecchi, Nicoletta Bertorello, F Petruzziello, Valentino Conter, Antonella Colombini, M. C. Putti, Raffaella Franca, Andrea Biondi, Concetta Micalizzi, Marco Rabusin, Franca Fagioli, Giuliana Decorti, Paola Rebora, Giuseppe Basso, Rosanna Parasole, Franca, Raffaella, Rebora, P., Bertorello, N., Fagioli, F., Conter, V., Biondi, A., Colombini, A., Micalizzi, C., Zecca, M., Parasole, R., Petruzziello, F., Basso, G., Putti, M. C., Locatelli, F., D'Adamo, ADAMO PIO, Valsecchi, M. G., Decorti, Giuliana, Rabusin, M., Franca, R, Rebora, P, Bertorello, N, Fagioli, F, Conter, V, Biondi, A, Colombini, A, Micalizzi, C, Zecca, M, Parasole, R, Petruzziello, F, Basso, G, Putti, M, Locatelli, F, D'Adamo, P, Valsecchi, M, Decorti, G, and Rabusin, M

Subjects
0301 basic medicine, Oncology, Male, Time Factors, Pharmacogenomic Variants, Gastrointestinal Diseases, medicine.medical_treatment, chemotherapy, 0302 clinical medicine, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Pyrophosphatases, Child, Glutathione Transferase, Clinical Trials as Topic, Pharmacogenetic, leukemia, Single Nucleotide, Induction Chemotherapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma, AIEOP-BFM ALL 2000, Phenotype, Treatment Outcome, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, 030220 oncology & carcinogenesis, Predictive value of tests, Child, Preschool, Molecular Medicine, Female, ITPA, Chemical and Drug Induced Liver Injury, Multidrug Resistance-Associated Proteins, Receptor, toxicitie, medicine.medical_specialty, Adolescent, Receptor, Adenosine A2A, acute lymphoblastic leukemia, Polymorphism, Single Nucleotide, Adenosine A2A, 03 medical and health sciences, children, Predictive Value of Tests, Internal medicine, medicine, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, Preschool, Retrospective Studies, Pharmacology, Chemotherapy, business.industry, Induction chemotherapy, Infant, Retrospective cohort study, Consolidation Chemotherapy, Gene Deletion, Logistic Models, Multiplex Polymerase Chain Reaction, Mutation, Nervous System Diseases, Pharmacogenetics, Pharmacogenomic Testing, 030104 developmental biology, Immunology, ALL, business
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.

Published
2015

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