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1.
Ann Oncol ; 25(2): 442-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24412823

RESUMO

BACKGROUND: [18F]fluorodeoxyglucose-positron emission tomography (PET) is emerging as a strong diagnostic and prognostic tool in follicular lymphoma (FL) patients. PATIENTS AND METHODS: In a subset analysis of the FOLL05 trial (NCT00774826), we investigated the prognostic role of post-induction PET (PI-PET) scan. Patients were eligible to this study if they had a PI-PET scan carried out within 3 months from the end of induction immunochemotherapy. Progression-free survival (PFS) was the primary study end point. RESULTS: A total of 202 patients were eligible and analysed for this study. The median age was 55 years (range 33-75). Overall, PI-PET was defined as positive in 49 (24%) patients. Conventional response assessment with CT scan was substantially modified by PET: 15% (22/145) of patients considered as having a complete response (CR) after CT were considered as having partial response (PR) after PI-PET and 53% (30/57) patients considered as having a PR after CT were considered as a CR after PI-PET. With a median follow-up of 34 months, the 3-year PFS was 66% and 35%, respectively, for patients with negative and positive PI-PET (P<0.001). At multivariate analysis, PI-PET (hazard ratio 2.57, 95% confidence interval 1.52-4.34, P<0.001) was independent of conventional response, FLIPI and treatment arm. Also, the prognostic role of PI-PET was maintained within each FLIPI risk group. CONCLUSIONS: In FL patients, PI-PET substantially modifies response assessment and is strongly predictive for the risk of progression. PET should be considered in further updates of response criteria.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluordesoxiglucose F18 , Linfoma Folicular/diagnóstico por imagem , Compostos Radiofarmacêuticos , Intervalo Livre de Doença , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tomografia por Emissão de Pósitrons , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
2.
Ann Oncol ; 25(7): 1404-1410, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24799461

RESUMO

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Estudos de Coortes , Feminino , Hepatite C/complicações , Humanos , Linfoma de Células B/complicações , Masculino , Pessoa de Meia-Idade
3.
Ann Oncol ; 21(6): 1189-1195, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19858084

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection has been linked to lymphoproliferative disorders. Marginal zone B-cell lymphoma (MZL) represents one of the most frequent lymphoma subtypes associated with HCV infection. We describe an unusual subset of HCV-associated MZL characterized by subcutaneous presentation. MATERIALS AND METHODS: A series of 12 HCV-positive patients presenting with subcutaneous nodules that revealed lymphoma infiltration at biopsy. Molecular analysis of immunoglobulin heavy chain (IGH) gene rearrangement and FISH investigations for t(11;18)(q21;q21) and t(14;18)(q32;q21) were carried out in nine patients. RESULTS: The 12 patients (median age 69.5 years), all with positive HCV serology, presented with single or multiple subcutaneous nodules resembling lipomas. Histologically the lesions showed lymphoid infiltrates, consistent with extranodal MZL of mucosa-associated lymphoid tissue (MALT). Functional IGH gene rearrangements were identified in nine tested patients, with somatic mutations in 82%, indicating a histogenesis from germinal center-experienced B cells. The t(11;18) was found in two of nine cases. Staging did not show any other lymphoma localization. In two patients, a response was achieved with antiviral treatment. Extracutaneous spread to MALT sites occurred in a case. CONCLUSIONS: Our observations expand the spectrum of HCV-associated lymphomas to include a subset of extranodal MZL characterized by a novel primary 'lipoma-like' subcutaneous presentation and indolent clinical course.


Assuntos
Hepatite C/diagnóstico , Lipoma/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Células B/diagnóstico , Tela Subcutânea/patologia , Idoso , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 18 , Diagnóstico Diferencial , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Hepacivirus/fisiologia , Hepatite C/complicações , Hepatite C/genética , Humanos , Lipoma/etiologia , Lipoma/genética , Lipoma/patologia , Linfoma de Células B/etiologia , Linfoma de Células B/genética , Linfoma de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias de Tecido Conjuntivo/diagnóstico , Neoplasias de Tecido Conjuntivo/etiologia , Neoplasias de Tecido Conjuntivo/genética , Neoplasias de Tecido Conjuntivo/patologia , Estudos Retrospectivos , Translocação Genética
4.
Ann Oncol ; 20(1): 129-36, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18718888

RESUMO

BACKGROUND: Among marginal zone lymphomas (MZLs), bone marrow (BM) involvement features are well established in the splenic marginal zone lymphoma (SMZL); few data are available for extranodal marginal zone lymphoma (EMZL) and nodal marginal zone lymphoma (NMZL). PATIENTS AND METHODS: Incidence and patterns of histologic BM involvement are studied in 120 MZL patients (48 SMZL, 59 EMZL, 13 NMZL) at onset and during follow-up; relationships between clinical features, BM histology and flow cytometry (FC) are analyzed. RESULTS: At diagnosis, BM involvement occurs in 90% SMZL, 22% EMZL and 54% NMZL (P<0.0001); at reevaluation, incidence raises to 96% in SMZL and 34% in EMZL. Concordance between histology and FC is found in 87% of cases; most discordant cases have positive histology but negative FC. SMZL and EMZL show a nodular BM infiltration; the interstitial pattern is frequent in NMZL (P<0.0001); sinusoidal localization is typical of SMZL, frequent in NMZL and occasional in EMZL (P=0.0001). Stage, leukemic disease, B symptoms, more than one extranodal involved site, splenomegaly, elevated beta2-microglobulin, serum monoclonal component, International Prognostic Index (IPI) and age-adjusted IPI are directly related to BM infiltration. CONCLUSIONS: The different prevalence of BM involvement in MZL subtypes reflects their heterogeneous dissemination modalities; histology seems more sensible than FC to detect BM infiltration; development of BM involvement during follow-up is typical of EMZL.


Assuntos
Neoplasias da Medula Óssea/epidemiologia , Neoplasias da Medula Óssea/secundário , Medula Óssea/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Medula Óssea/patologia , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Incidência , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Leukemia ; 26(7): 1654-62, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22307176

RESUMO

The precise molecular pathogenesis of splenic marginal zone lymphoma (SMZL) is still unknown. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases.We performed a large-scale microRNA (miRNA) expression profiling analysis of 381 miRNAs by quantitative reverse transcription PCR (Q-RT-PCR) of 26 microdissected splenic tissue samples (7 HCV(+) SMZL; 8 HCV(-) SMZL and 11 non-neoplastic splenic controls). Single assay Q-RT-PCR and miRNA in situ hybridization (miRNA-ISH) were used to confirm the results in an independent cohort. Unsupervised hierarchical clustering of miRNA expression profiles demonstrated a distinct signature of SMZL compared with the normal splenic marginal zone. Supervised analysis revealed differentially expressed miRNAs, including miRNAs with previously recognized tumor suppressive or oncogenic potential. Five miRNAs were found significantly overexpressed in SMZL, including miR-21, miR-155 and miR-146a, whereas seven miRNAs showed significantly reduced expression, including miR-139, miR-345, miR-125a and miR-126. Furthermore, we identified miR-26b, a miRNA known to have tumor suppressive properties, as significantly downregulated in SMZL arising in HCV-positive patients (P=0.0016). In conclusion, there is a characteristic dysregulation of miRNA expression in SMZL with a possible implication in its molecular tumorigenesis.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Hepacivirus/isolamento & purificação , Hepatite C Crônica/genética , Linfoma de Zona Marginal Tipo Células B/genética , MicroRNAs/genética , Neoplasias Esplênicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite C Crônica/virologia , Humanos , Hibridização In Situ , Linfoma de Zona Marginal Tipo Células B/virologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/metabolismo , Baço/patologia , Neoplasias Esplênicas/virologia , Adulto Jovem
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