1. Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol
- Author
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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 C, Locatelli, F, d'Adamo, P, Valsecchi, M G, Decorti, G, and Rabusin, M
- 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-M1and GST-T1by 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 ITPArs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1rs246240 and ADORA2Ars2236624 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
- 2017
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