RESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Gastroenteropatias/genética , Doenças do Sistema Nervoso/genética , Farmacogenética/métodos , Variantes Farmacogenômicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Quimioterapia de Consolidação/efeitos adversos , Feminino , Gastroenteropatias/induzido quimicamente , Deleção de Genes , Predisposição Genética para Doença , Glutationa Transferase/genética , Humanos , Quimioterapia de Indução/efeitos adversos , Lactente , Modelos Logísticos , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Reação em Cadeia da Polimerase Multiplex , Mutação , Doenças do Sistema Nervoso/induzido quimicamente , Testes Farmacogenômicos/métodos , Fenótipo , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Valor Preditivo dos Testes , Pirofosfatases/genética , Receptor A2A de Adenosina/genética , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Prognosis for patients with malignant peritoneal mesothelioma is very poor, and most patients are beyond cure by the time the diagnosis has been made. The pathogenesis of this uncommon neoplasm seems to be related to asbestos and radiation exposure. The authors report a case of diffuse peritoneal mesothelioma in a 33-year-old man. Since the patient complained of aspecific symptoms and both biochemical and "imaging" studies did not provide useful informations for a definitive diagnosis, an exploratory laparotomy was performed. Intraoperative histological findings demonstrated the presence of a malignant peritoneal mesothelioma which had spread all over the omentum; considering the inoperability assessment of this case, the operation was completed and the patient was dismissed with an adjuvant chemo-therapy. Five weeks later the patient died.