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1.
Br J Haematol ; 185(3): 480-491, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30793290

RESUMO

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

2.
Br J Haematol ; 178(5): 699-708, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28782811

RESUMO

The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1-3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5-4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3-6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4-12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5-10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1-4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.


Assuntos
Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/patologia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transformação Celular Neoplásica/efeitos dos fármacos , Progressão da Doença , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Espanha/epidemiologia , Análise de Sobrevida , Adulto Jovem
3.
Clin Nucl Med ; 42(8): 595-602, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28604477

RESUMO

OBJECTIVES: To compare staging correctness between contrast-enhanced FDG PET/ceCT and 64-slice multi-detector-row CT (ceCT64) for initial staging and response evaluation at the end of treatment (EOT) in patients with Hodgkin lymphoma, diffuse large B cell lymphoma (DLBCL), and follicular lymphoma. METHODS: This prospective study compared initial staging and response evaluation at EOT. One hundred eighty-one patients were randomly assigned to either ceCT64 or FDG PET/ceCT. A nuclear medicine physician and a radiologist read FDG PET/ceCT scans independently and achieved post hoc consensus, whereas another independent radiologist interpreted ceCT64 separately. The reference standard included all clinical information, all tests, and follow-up. Ethics committees of the participating centers approved the study, and all participants provided written consent. RESULTS: Ninety-one patients were randomized to ceCT64 and 90 to FDG PET/ceCT; 72 had Hodgkin lymphoma, 72 had DLBCL, and 37 had follicular lymphoma. There was excellent correlation between the reference standard and initial staging for both FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84), although evaluation of the response at EOT was excellent only for FDG PET/ceCT (κ = 0.91). CONCLUSIONS: Our study demonstrated satisfactory agreement between FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84) in initial staging compared with the reference standard (P = 0.16). Response evaluation at EOT with FDG PET/ceCT (κ = 0.91) was superior compared with ceCT64 (κ = 0.307) (P < 0.001).


Assuntos
Meios de Contraste , Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Linfoma/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/instrumentação , Estudos Prospectivos , Resultado do Tratamento
4.
Clin Lymphoma Myeloma Leuk ; 15(7): 398-403, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25843416

RESUMO

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing a highly variable outcome. In patients with DLBCL relapsed/refractory to first-line treatment with rituximab the usefulness of the revised International Prognostic Index (R-IPI) as a prognostic tool remains unexplored. Some biological parameters (B-cell lymphoma 6 [Bcl-6], Bcl-2, p53, and multiple myeloma 1 [MUM1]) and blood populations (lymphocyte and monocyte counts) have been described as International Prognostic Index-independent prognostic factors. The objective was to evaluate the R-IPI to predict the outcome of DLBCL patients at the time of relapse after a front-line treatment with chemotherapy and rituximab and to establish in this population the relationship between biological parameters and outcome. PATIENTS AND METHODS: We included patients with refractory/relapsed DLBCL after first-line treatment with rituximab-containing regimens; patients must have already finished a rescue treatment also including rituximab. Immunohistochemical assessment of Bcl-2, Bcl-6, p53, and MUM1 expression were undertaken in available biopsies. R-IPI factors were identified from the clinical data at diagnosis and at relapse. Response was assessed using National Cancer Institute-sponsored Working Group guidelines. RESULTS: R-IPI prognosis at relapse was not significantly associated with overall response rate (ORR) after Rituximab-chemotherapy rescue therapy. None of the immunohistochemical parameters analyzed correlated with rescue therapy results. In contrast, patients with absolute lymphocyte count (ALC) ≥ 1 × 10(9)/L at relapse were more likely to respond than patients with ALC < 1 × 10(9)/L (P = .05). CONCLUSION: The R-IPI score calculated at relapse could not predict the ORR to second-line treatment. Lymphopenia is a simple and useful predictor for outcome in relapsed/refractory DLBCL and the only prognostic factor that in our hands could predict the overall response to a second-line treatment with rituximab and chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Linfoma Difuso de Grandes Células B/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Rituximab/uso terapêutico , Adulto , Idoso , Biópsia , Estudos Transversais , Feminino , Genes bcl-2/genética , Humanos , Fatores Reguladores de Interferon/metabolismo , Contagem de Linfócitos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Fragmentos de Peptídeos/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Proteína Supressora de Tumor p53/metabolismo
5.
Am J Dermatopathol ; 37(6): 499-502, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25014106

RESUMO

Cutaneous manifestation as the first sign of Hodgkin lymphoma (HL) is very rare and diagnostically challenging; especially, because the clinical presentation of specific skin involvement by HL is polymorphous. We present a 44-year-old man with erythematous indurate papules and plaques in the right forearm and arm where skin biopsy showed an HL. He also has an enlarged epitrochlear node, and later histopathologic study confirmed the diagnosis of HL subtype-mixed cellularity. Immunohistochemical stains in both biopsies showed that the atypical cells were positive for CD30 and CD15, and negative for CD20 and CD3. PAX5 stained the nuclei of the atypical large lymphoid cells weakly and Oct-2 staining was negative in the atypical cells. EBER and LMP1 protein were negative in both biopsies. Epitrochlear involvement in HL, like in our case, is a rare event (<1%). We reviewed data about prognosis, clinical appearance, and treatment of all the cases of HL specific skin involvement published after Sioutos et al, emphasizing the cases where HL specific skin involvement was the first sign of the disease as in our patient.


Assuntos
Doença de Hodgkin/patologia , Metástase Linfática/patologia , Neoplasias Cutâneas/patologia , Adulto , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Masculino
6.
J Cutan Pathol ; 39(12): 1125-30, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23043641

RESUMO

The coexistence of skin-limited Langerhans cell histiocytosis (LCH) and Rosai-Dorfman disease (RDD) is an exceptional finding. The association of lymphomas and histiocytosis is also infrequent. We report the case of a 68-year-old man which presented an exceptional association of cutaneous LCH and RDD and splenic marginal zone lymphoma. He was stable for few years. Suddenly, the patient was admitted into Hematology Department with a remarkable enlargement of spleen and liver without enlargement of lymphadenopathies or skin lesions flare. He died 24 h later despite treatment with systemic chemotherapy combined with prednisone. Pre-mortem biopsy showed infiltration with histiocytic sarcoma. We think that a transdifferentiation phenomenon could explain our case, although we could not show a clonal relationship between the cutaneous and the liver diseases. We also want to pay attention to the fact that a fast transformation to a more aggressive disease can occur long time after the presentation of the first lesion, a problem that stresses the importance of performing a close and permanent follow-up of these patients.


Assuntos
Sarcoma Histiocítico/complicações , Histiocitose de Células de Langerhans/complicações , Histiocitose Sinusal/complicações , Neoplasias Hepáticas/complicações , Linfoma de Zona Marginal Tipo Células B/complicações , Segunda Neoplasia Primária , Neoplasias Esplênicas/complicações , Idoso , Evolução Fatal , Sarcoma Histiocítico/patologia , Histiocitose de Células de Langerhans/patologia , Histiocitose Sinusal/patologia , Humanos , Neoplasias Hepáticas/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Neoplasias Esplênicas/patologia
7.
Mod Pathol ; 24(5): 698-707, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21240256

RESUMO

Follicular lymphoma (FL) is one of the most common forms of the low-grade non-Hodgkin's lymphoma in adults, with a characteristic translocation, t(14;18)(q32;q21) that deregulates the expression of the BCL2 gene. The clinical course of FL patients is variable, whereby a subset of patients survive for long periods even without relapses, whereas the majority have frequent relapses with shorter survival. We have analyzed a series of 186 FLs, studying the correlation between clinical outcome and the tumor cell expression of a set of immunohistochemical markers, using an automated procedure for tissue microarrays to reduce the subjectivity of scoring. The results identified several markers associated with differences in overall survival (OS) in univariate analyses, such as Cyclin E, Mdm2, CD10, p21, IgD, Bcl-xL, CD30, and E2F6. Cases with a higher level of expression of Cyclin E, Mdm2, p21, IgD, Bcl-xL, CD30, and E2F6 were associated with a significantly shorter OS. On the other hand, strong CD10 expression was linked to a significantly better outcome. A Cox model was then constructed, integrating the Follicular Lymphoma International Prognostic Index (FLIPI) score and a restricted selection of three immunohistochemical markers: Cyclin E, Mdm2, and CD10 expression. A potentially useful finding is that the integrated FLIPI plus immunohistochemical model can be used to identify a subset of 26 patients (almost 20% of the total series), with a survival probability of 100% at 5 years. This not only confirms that a group of FL cases may have a very good clinical course, but also indicates that this group can be identified using this integrated clinical and immunohistochemical approach.


Assuntos
Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica/métodos , Linfoma Folicular/diagnóstico , Linfoma Folicular/metabolismo , Proteínas de Neoplasias/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Espanha/epidemiologia , Taxa de Sobrevida , Análise Serial de Tecidos , Adulto Jovem
8.
Blood ; 111(1): 351-8, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17898315

RESUMO

GCET1 (germinal center B cell-expressed transcript-1) gene codes for a serpin expressed in germinal center (GC) B cells. Following the observation that follicular lymphoma cases exhibit an increased level of Gcet1 expression, compared with follicular hyperplasia, we have characterized Gcet1 protein expression in human tissues, cell lines, and a large series of lymphomas. To this end, we have performed immunohistochemical and Western blot analyses using a newly generated monoclonal antibody that is reactive in paraffin-embedded tissues. Our results demonstrate that Gcet1 is expressed exclusively by neoplasms hypothetically to be arrested at the GC stage of differentiation, including follicular lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and a subset of diffuse large B-cell lymphoma, T-cell/histiocyte rich B-cell lymphoma, and Burkitt lymphoma. Within these tumors, Gcet-1 protein expression is restricted to a subset of GC B cells, establishing the existence of a distinct heterogeneity among normal and neoplastic GC B cells. None of the other B-cell lymphomas, that is, chronic lymphocytic leukemia, splenic marginal zone lymphoma, and mantle cell lymphoma, was Gcet1(+), which underlines the potential utility of Gcet1 expression in lymphoma diagnosis. The results of RNA and protein expression should prompt further investigation into the role of Gcet1 in regulating B-cell survival.


Assuntos
Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Centro Germinativo/patologia , Linfoma/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Serpinas/genética , Serpinas/metabolismo , Western Blotting , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Linhagem Celular Tumoral , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Técnicas Imunoenzimáticas , Linfoma/genética , Linfoma/metabolismo , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma Folicular/genética , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Análise de Sequência com Séries de Oligonucleotídeos
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