RESUMO
Wilms' tumor gene 1 (WT1) is gaining increasing attention as a therapeutic target molecule due to its common expression in acute leukemias and its involvement in cell proliferation. Here, we reported on WT1 messenger RNA expression levels at diagnosis in a series of 238 adult acute lymphoblastic leukemia (ALL) samples of various subtypes and clinical outcome. WT1 expression was found in 219 out of 238 ALL samples (92%). Compared to a cohort of acute myeloid leukemia patients, the median WT1 expression level in ALL was significantly lower with large variations among different ALL subgroups. Specifically, WT1 expression levels were low in mature B-ALL and highest in ALL cases with co-expression of myeloid markers, making it a useful therapeutic target molecule in adult ALL with the exception of mature B-ALL. Cox regression analysis, considering ALL phenotype as well as molecular-cytogenetic subsets, revealed no independent prognostic role of WT1 expression level for disease-free and overall survival.
Assuntos
Regulação Leucêmica da Expressão Gênica , Genes do Tumor de Wilms , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Proteínas WT1 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resultado do Tratamento , Proteínas WT1/genética , Proteínas WT1/metabolismo , Adulto JovemRESUMO
This study was performed to investigate hematotoxicity and occurrence of PPE in patients with high-grade non-Hodgkins lymphoma treated with a modified CHOP regimen (CLAOP), where doxorubicin had been substituted by a noncardiotoxic pegliposomal doxorubicin. An open-label phase I/IIa study was performed evaluating CLAOP21/20 with 20 mg/m(2) of pegliposomal doxorubicin every 21 days (12 patients), and a dose-dense filgrastim supported CLAOP14 regimen every 14 days with escalating doses of pegliposomal doxorubicin (24 patients) in elderly high-grade lymphoma patients or patients with comorbidity interfering with cardiac function. CLAOP21/20 was well tolerated. Hematotoxicity was similar to that reported with regular CHOP. In the CLAOP14 cohort, a pegliposomal doxorubicin dose of 25 mg/m(2) was associated with dose-limiting hematotoxicity, febrile episodes, and PPE. Both regimens were active with an overall response rate of 60% and 77%, respectively. The recommended dose of pegliposomal doxorubicin in the biweekly regimen for Phase II/III testing is 20 mg/m(2).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Coração/efeitos dos fármacos , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Proteínas Recombinantes , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Vinorelbine was added to carboplatin plus paclitaxel to determine efficacy and toxicity in non-small cell lung cancer (NSCLC) patients with good performance status. PATIENTS AND METHODS: Vinorelbine 30 mg/m2 plus paclitaxel 175 mg/m2 plus carboplatin AUC 5 was administered every three weeks for a maximum of 6 cycles. RESULTS: One out of 37 patients had a complete and 12 a partial remission (35% response rate). Six patients (16%) had disease stabilization and 18 (49%) progressed. Grade III or IV neutropenia occurred in 11 (30%) and febrile neutropenia in 6 (16%) patients. Grade III/IV neuropathy was observed in 6 (16%) patients. The median time to progression was 6 months (95% CI 4.0 - 8.0), and median survival 11 months (95% CI 8.3 - 13.7). One- and two-year survival was 41% (95% CI 24 - 58) and 24% (95% CI 8.7 - 39.1), respectively. CONCLUSION: This triple-chemotherapy combination is feasible. The response rates justify further investigation in similar patient subgroups.
