Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol.
Pharmacogenomics J
; 17(1): 4-10, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-26644204
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.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Farmacogenética
/
Protocolos de Quimioterapia Combinada Antineoplásica
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Enfermedad Hepática Inducida por Sustancias y Drogas
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Variantes Farmacogenómicas
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Enfermedades Gastrointestinales
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Enfermedades del Sistema Nervioso
Tipo de estudio:
Etiology_studies
/
Guideline
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Italia