Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.596
Filtrar
1.
Anticancer Res ; 40(12): 6685-6697, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33288562

RESUMO

BACKGROUND/AIM: Follicular lymphoma (FL) relapse within 24 months of the first immunochemotherapy (POD24) indicates more precisely poor overall survival and high risk of death. The aim of the study was to assess the potential value of POD24 in FL and describe the enhancer of zeste homolog 2 (EZH2) expression profile, in correlation with clinical/histopathological/immunophenotypical characteristics. MATERIALS AND METHODS: This retrospective single-center study included 75 patients with FL treated under watch and wait (W&W) and immunochemotherapy regimens. All cases were immunohistochemically assessed: assays were performed for EZH2, CD10, BCL6, BCL2, MUM1, MYC and p53. RESULTS: POD24 was independent of clinical/histopathological/immunohistochemical features and separated patients with inferior outcomes. EZH2 high expression was observed in high/low grade and follicular/diffuse FL patterns. BCL2-negative (p=0.042) and MUM1 (p=0.039), MYC (p<0.001), p53 (p<0.001) - positive cases had significantly higher EZH2 expression. CONCLUSION: POD24 is currently the most useful tool for the identification of poor outlook patients. EZH2 is crucial in FL biology, but the value of its protein expression is limited as a prognostic factor.


Assuntos
Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Idoso , Estudos de Coortes , Feminino , Humanos , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de Sobrevida
2.
Lancet Oncol ; 21(11): 1433-1442, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33035457

RESUMO

BACKGROUND: Activating mutations of EZH2, an epigenetic regulator, are present in approximately 20% of patients with follicular lymphoma. We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma. METHODS: This study was an open-label, single-arm, phase 2 trial done at 38 clinics or hospitals in France, the UK, Australia, Canada, Poland, Italy, Ukraine, Germany, and the USA. Eligible patients were adults (≥18 years) with histologically confirmed follicular lymphoma (grade 1, 2, 3a, or 3b) that had relapsed or was refractory to two or more systemic therapies, had an Eastern Cooperative Oncology Group performance status of 0-2, and had sufficient tumour tissue for central testing of EZH2 mutation status. Patients were categorised by EZH2 status: mutant (EZH2mut) or wild-type (EZH2WT). Patients received 800 mg of tazemetostat orally twice per day in continuous 28-day cycles. The primary endpoint was objective response rate based on the 2007 International Working Group criteria for non-Hodgkin lymphoma, assessed by an independent radiology committee. Activity and safety analyses were done in patients who received one dose or more of tazemetostat. This study is registered with ClinicalTrials.gov, NCT01897571, and follow-up is ongoing. FINDINGS: Between July 9, 2015, and May 24, 2019, 99 patients (45 in the EZH2mut cohort and 54 in the EZH2WT cohort) were enrolled in the study. At data cutoff for the analysis (Aug 9, 2019), the median follow-up was 22·0 months (IQR 12·0-26·7) for the EZH2mut cohort and 35·9 months (24·9-40·5) for the EZH2WT cohort. The objective response rate was 69% (95% CI 53-82; 31 of 45 patients) in the EZH2mut cohort and 35% (23-49; 19 of 54 patients) in the EZH2WT cohort. Median duration of response was 10·9 months (95% CI 7·2-not estimable [NE]) in the EZH2mut cohort and 13·0 months (5·6-NE) in the EZH2WT cohort; median progression-free survival was 13·8 months (10·7-22·0) and 11·1 months (3·7-14·6). Among all 99 patients, treatment-related grade 3 or worse adverse events included thrombocytopenia (three [3%]), neutropenia (three [3%]), and anaemia (two [2%]). Serious treatment-related adverse events were reported in four (4%) of 99 patients. There were no treatment-related deaths. INTERPRETATION: Tazemetostat monotherapy showed clinically meaningful, durable responses and was generally well tolerated in heavily pretreated patients with relapsed or refractory follicular lymphoma. Tazemetostat is a novel treatment for patients with follicular lymphoma. FUNDING: Epizyme.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Benzamidas/administração & dosagem , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Linfoma Folicular/tratamento farmacológico , Piridonas/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/efeitos adversos , Feminino , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Piridonas/efeitos adversos , Resultado do Tratamento
3.
Exp Hematol ; 91: 55-64, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32966868

RESUMO

In this study, we examined the suitability of visible and infrared (Vis-NIR) hyperspectral imaging (HSI) for the quantification of prognostic markers in non-Hodgkin lymphoma on the example of the Ki67 proliferation index. Ki67 quantification was done on six follicular lymphomas (FLs) and 12 diffuse large B-cell lymphomas (DLBCLs) by applying classic immunohistochemistry. The Ki67 index was comparatively assessed visually, using HSI-based quantification and a digital imaging analysis (DIA) platform. There was no significant difference between visual assessment (VA), DIA, and HSI in FLs. For DLBCLs, VA resulted in significantly higher Ki67 values than HSI (p = 0.023) and DIA (p = 0.006). No such difference was seen comparing analysis by HSI and DIA (p = 0.724). Cohen's κ revealed a "substantial correlation" of Ki67 values for HSI and DIA in FLs and DLBCLs (κ = 0.667 and 0.657). Here we provide the first evidence that, comparably to traditional DIA, HSI can be used reliably to quantify protein expression, as exemplified by the Ki67 proliferation index. By covering the near-infrared spectrum, HSI might offer additional information on the biochemical composition of pathological specimens, although our study could not show that HSI is clearly superior to conventional DIA. However, the analysis of multiplex immunohistochemistry might benefit from such an approach, especially if overlapping immunohistochemical reactions were possible. Further studies are needed to explore the impact of this method on the analysis and quantification of multiple marker expression in pathological specimens.


Assuntos
Antígenos de Neoplasias/análise , Antígeno Ki-67/análise , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma de Burkitt/diagnóstico por imagem , Linfoma de Burkitt/patologia , Proliferação de Células , Análise Custo-Benefício , Humanos , Raios Infravermelhos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Índice Mitótico , Projetos Piloto , Prognóstico , Processamento de Sinais Assistido por Computador
4.
Hematol Oncol ; 38(5): 673-679, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32835439

RESUMO

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle-related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.


Assuntos
Biomarcadores Tumorais , Citocinas/genética , Centro Germinativo/patologia , Linfoma Folicular/etiologia , Linfoma Folicular/patologia , Idoso , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias
5.
Jpn J Clin Oncol ; 50(12): 1395-1402, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-32856068

RESUMO

OBJECTIVE: Idelalisib is an orally administered, highly selective inhibitor of phosphatidylinositol 3-kinase-δ. In this phase 1b study, the safety, tolerability and pharmacokinetics of idelalisib, an oral inhibitor of phosphatidylinositol 3-kinase-δ, were evaluated in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma. METHODS: In total, six patients (follicular lymphoma: n = 3, chronic lymphocytic leukemia: n = 3) were enrolled to receive idelalisib 150 mg twice daily. RESULTS: No dose-limiting toxicities were reported. The most common adverse events were diarrhea (n = 5), gastritis (n = 3), insomnia (n = 3) and pyrexia (n = 3). The most common ≥grade 3 adverse events were diarrhea (n = 2), increased transaminase levels (n = 2) and decreased appetite (n = 2). The maximum idelalisib plasma concentrations (Cmax) were achieved at 2.50 h (range: 1.50-4.00 h). The mean idelalisib plasma concentrations decreased over time but remained detectable in most patients at 12 h. All enrolled patients underwent efficacy evaluation by investigators, and five patients (follicular lymphoma: n = 2, chronic lymphocytic leukemia: n = 3) achieved partial response. The median duration of partial response was 14.5 months (range: 3.7-31.3 months). CONCLUSION: Idelalisib 150 mg twice daily was considered tolerable in Japanese patients with follicular lymphoma or chronic lymphocytic leukemia.(Clinical trial registration: NCT02242045).


Assuntos
Antineoplásicos/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Purinas/administração & dosagem , Quinazolinonas/administração & dosagem , Administração Oral , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Esquema de Medicação , Humanos , Japão , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Purinas/efeitos adversos , Purinas/farmacocinética , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacocinética , Recidiva , Segurança , Resultado do Tratamento
6.
Ann Hematol ; 99(10): 2441-2443, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32808104
7.
Int J Hematol ; 112(5): 658-665, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32740764

RESUMO

The incidence and clinical characteristics of histological transformation (HT) from duodenal type follicular lymphoma (DFL) are unclear. A retrospective analysis was conducted to identify the incidence and clinical features of HT from DFL in 23 cases with DFL. The median follow-up duration was 4.6 years (range, 0.8-20 years). HT to diffuse large B-cell lymphoma was observed in 2 of 23 cases during follow-up (8.7%). One of two cases transformed at 21 months later with increased serum lactate dehydrogenase (LDH; 1655 U/L) and abdominal lymphadenopathy. Partial response was achieved after R-THP (pirarubicin)-COP therapy, but the disease progressed. The other case transformed at 8.3 years with an increase of serum LDH (4022 U/L), abdominal lymphadenopathy, and bone marrow involvement. The disease was refractory to DA-EPOCH-R and a high-dose methotrexate/cytarabine regimen. The patient received allogenic peripheral blood stem cell transplantation and finally achieved complete response. Both cases developed HT at nodal or other intestinal lesions with no progression of the primary duodenal lesion. No significant factors for the occurrence of HT were identified. Although the incidence is low, HT could occur in DFL with aggressive clinical manifestations.


Assuntos
Transformação Celular Neoplásica/patologia , Neoplasias Duodenais/patologia , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Neoplasias Duodenais/terapia , Feminino , Seguimentos , Humanos , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo
9.
Int J Hematol ; 112(2): 136-138, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32506320

RESUMO

Diffuse follicular lymphoma (FL) variant is a rare condition that shows distinctive clinical, morphological, immunophenotypic, and molecular features that distinguish it from classical FL. Diffuse FL variant is characterized by a predominantly diffuse growth pattern, absence of the t (14;18) IGH/BCL2 translocation, CD23 expression, and presence of 1p36 deletion. Gene mutations involving STAT6 have been reported, with nuclear expression of STAT6 and phosphorylated STAT6 detected by immunohistochemistry. Patients frequently present with inguinal node involvement and low clinical stage. We describe the case of an 80-year-old female diagnosed with diffuse FL variant, presented with a classic diagnostic pattern and an unusual aggressive clinical onset.


Assuntos
Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Idoso de 80 Anos ou mais , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Linfonodos/patologia , Linfoma Folicular/imunologia , Linfoma Folicular/patologia , Mutação , Fosforilação , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas c-bcl-2/genética , Doenças Raras , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Translocação Genética
10.
Int J Lab Hematol ; 42(4): 453-463, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32364682

RESUMO

INTRODUCTION: Histopathological examination and immunohistochemistry (IHC) with a crucial role of CD10 expression remain a standard diagnostic tool in follicular lymphoma (FL). The results of IHC CD10 detection with different primary antibodies are not fully reproducible, but some reports show that flow cytometry (FCM) can be a reliable method of CD10 identification. METHODS: The aim of the study was to compare results of CD10 expression in FL by IHC and FCM including immunophenotypic features in the context of the BCL2 and BCL6 alterations. RESULTS: Out of 76 histopathologically diagnosed FL, a group of 25 cases had simultaneously FCM. Immunohistochemically 77.6% of cases were CD10-positive with comparable and reproducible results to FCM. Differences between the FCM expression of CD5/CD10/CD11c/CD25/CD43 and BCL2 overexpression (BCL2(+)higher ) correlated with the BCL2 and BCL6 rearrangements (R) status. Lack of CD10 expression corresponded with the absence of BCL2R and higher MUM1 expression by IHC results but had no clinical impact on the long-time outcomes. CONCLUSIONS: Immunohistochemistry staining is a comparable method to FCM assessment in the evaluation of CD10 expression and diagnosis of FL. Fine-needle aspiration biopsy/FCM (FNAB/FCM) could be a useful tool for verifying FL diagnosis and CD10 detection. Despite its heterogeneity, FL has a characteristic immunophenotype. BCL2R and BCL6R FL cases differ mainly in levels of BCL2 and CD10 with CD43 co-expression; BCL2(+)higher by FCM correlates with BCL2R. Moreover, FNAB plays an important role in material provision for supportive karyotyping and BCL2R, BCL6R assessed by FISH.


Assuntos
Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Rearranjo Gênico , Imuno-Histoquímica , Linfoma Folicular , Neprilisina , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-6 , Feminino , Humanos , Linfoma Folicular/sangue , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Neprilisina/sangue , Neprilisina/genética , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/sangue , Proteínas Proto-Oncogênicas c-bcl-6/genética
11.
Ann Hematol ; 99(7): 1595-1604, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32417940

RESUMO

Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma with heterogeneous outcomes. Progression or relapse of FL within 2 years (so-called POD24) after diagnosis is associated with a poor outcome for patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) in clinical trials. POD24 needs further validation before it can be used as a relevant endpoint to assess treatment efficacy. In the present retrospective monocentric study, we investigated the predictive value of POD24 in a cohort of grade 1, 2, or 3a FL patients treated in our institution (Nantes Medical University, France) and registered in our local database. We investigated the nature of treatment lines, patients' outcomes, and the prognostic value of POD24. Between 2007 and 2016, 317 patients were included. After first-line therapy, 60 patients relapsed within 2 years (POD24-pos cohort), and 254 patients did not relapse within 2 years (PO24-neg cohort). Thirty-three patients died, and 34 patients had an aggressive transformation. The median follow-up is 59.9 months (1.6-395.5). The median PFS is 59.9 months. Overall survival (OS) at 1 year, 3 years, and 5 years is 98.4% [97.0-99.8], 95.1% [92.6-97.6], and 92.5% [89.3-95.9], respectively. The 5-year OS was statistically lower for POD24-pos patients (82% [71.9-93.5]) than for POD24-neg patients (93.3% [88.98-97.8]) (p = 10-5). In multivariate analyses, transformation was predictive of OS, and PS (≥ 1) was predictive of POD24. POD24 is predictive of a worse OS and may be recommended as a relevant endpoint in clinical trials and in real life in particular for patients with advanced disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Progressão da Doença , Doxorrubicina/administração & dosagem , Feminino , França/epidemiologia , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prednisona/administração & dosagem , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vincristina/administração & dosagem
12.
Lab Invest ; 100(10): 1300-1310, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32472096

RESUMO

A pathological evaluation is one of the most important methods for the diagnosis of malignant lymphoma. A standardized diagnosis is occasionally difficult to achieve even by experienced hematopathologists. Therefore, established procedures including a computer-aided diagnosis are desired. This study aims to classify histopathological images of malignant lymphomas through deep learning, which is a computer algorithm and type of artificial intelligence (AI) technology. We prepared hematoxylin and eosin (H&E) slides of a lesion area from 388 sections, namely, 259 with diffuse large B-cell lymphoma, 89 with follicular lymphoma, and 40 with reactive lymphoid hyperplasia, and created whole slide images (WSIs) using a whole slide system. WSI was annotated in the lesion area by experienced hematopathologists. Image patches were cropped from the WSI to train and evaluate the classifiers. Image patches at magnifications of ×5, ×20, and ×40 were randomly divided into a test set and a training and evaluation set. The classifier was assessed using the test set through a cross-validation after training. The classifier achieved the highest levels of accuracy of 94.0%, 93.0%, and 92.0% for image patches with magnifications of ×5, ×20, and ×40, respectively, in comparison to diffuse large B-cell lymphoma, follicular lymphoma, and reactive lymphoid hyperplasia. Comparing the diagnostic accuracies between the proposed classifier and seven pathologists, including experienced hematopathologists, using the test set made up of image patches with magnifications of ×5, ×20, and ×40, the best accuracy demonstrated by the classifier was 97.0%, whereas the average accuracy achieved by the pathologists using WSIs was 76.0%, with the highest accuracy reaching 83.3%. In conclusion, the neural classifier can outperform pathologists in a morphological evaluation. These results suggest that the AI system can potentially support the diagnosis of malignant lymphoma.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador/métodos , Linfoma/diagnóstico , Algoritmos , Diagnóstico por Computador/estatística & dados numéricos , Técnicas Histológicas , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Linfoma Folicular/diagnóstico , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Redes Neurais de Computação , Variações Dependentes do Observador , Patologistas , Pseudolinfoma/diagnóstico , Pseudolinfoma/diagnóstico por imagem , Pseudolinfoma/patologia
13.
Cancer Cell ; 37(5): 655-673.e11, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32396861

RESUMO

Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.


Assuntos
Linfócitos B/imunologia , Transformação Celular Neoplásica/imunologia , Reprogramação Celular , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Linfoma de Células B/imunologia , Linfoma Folicular/imunologia , Mutação , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Humanos , Linfoma de Células B/genética , Linfoma de Células B/patologia , Linfoma Folicular/genética , Linfoma Folicular/patologia , Camundongos , Camundongos Endogâmicos C57BL
14.
Tumori ; 106(6): NP5-NP8, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32442038

RESUMO

BACKGROUND: Follicular lymphoma (FL) is characterized by frequent relapses and need for multitude lines of therapy, which includes different immunochemotherapy regimens, novel monoclonal antibodies, novel drugs, and autologous or allogenic stem cell transplant. Early use of autologous stem cell transplantation (ASCT) improves prognosis in patients with FL who may be candidates for an aggressive approach. CASE PRESENTATION: We report the case of a 49-year-old woman with thrombophilia with relapsed/refractory grade 3A FL, heavily pretreated, who achieved third complete remission after high-dose chemotherapy and ASCT, despite experiencing life-threatening adverse events during her treatment history. CONCLUSIONS: Stem cell transplantation has emerged as the standard of care for young patients with FL but may be effective also in complex and multirelapsed clinical cases.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recidiva , Retratamento , Transplante Autólogo , Resultado do Tratamento
15.
Ann Hematol ; 99(7): 1627-1634, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32451707

RESUMO

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Rituximab/administração & dosagem , Terapia de Salvação/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva , Estudos Retrospectivos , Rituximab/efeitos adversos , Espanha/epidemiologia , Análise de Sobrevida , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
16.
PLoS One ; 15(5): e0233449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442224

RESUMO

Follicular lymphoma (FL) is an indolent neoplasia comprising approximately 20% of lymphomas. FL is generally considered incurable, with a median survival exceeding 10 years. A subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, resulting in markedly poorer clinical outcome, with a reduced median survival after transformation of 1-2 years. Early, reliable prediction of HT would be valuable in the clinical setting, allowing pre-emptive therapeutic intervention. We previously used proteomics to identify the glycolytic enzymes fructose-bisphosphate aldolase A (aldolase A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as candidate predictors of FL transformation. Now, we use immunohistochemistry to evaluate expression of these enzymes in paired primary FLs from patients with (n = 41) or without subsequent HT (n = 49), to test their value as predictive biomarkers. At initial FL diagnosis, patients with subsequent HT had significantly higher expression of aldolase A and GAPDH (p<0.001 and p<0.01) compared with patients without HT. Furthermore, high expression of aldolase A and GAPDH was associated with significantly shorter transformation free survival (p = 0.018, p = 0.001). These data suggest that high expression of aldolase A and GAPDH, may indicate increased metabolic turnover, and that these enzymes may be useful biomarkers in primary FL for predicting the risk of subsequent lymphoma transformation.


Assuntos
Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Frutose-Bifosfato Aldolase/metabolismo , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Glicólise , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Int J Lab Hematol ; 42(4): 431-438, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32343486

RESUMO

INTRODUCTION: Bendamustine has been reported to be effective against low-grade B-cell lymphoma. We examined the effect of bendamustine on the lymphocyte-monocyte ratio (LMR) in low-grade B-cell lymphoma patients. METHODS: We retrospectively reviewed 127 cases of first line or relapse/refractory low-grade B-cell lymphoma in three individual institutions (Asahikawa Municipal Hospital, Aiiku Hospital, and Hakodate Municipal Hospital). Only patients who had received at least three courses of bendamustine therapy were selected; the LMR was evaluated at starting the initial course of bendamustine therapy. Time to next treatment (TTNT) was used to ascertain the efficacy of bendamustine therapy. RESULTS: Follicular lymphoma (FL), at 68.5% (87/127), is the most common histological subtype of low-grade B-cell lymphoma. The receiver operating characteristic (ROC) curve for the LMR showed a cutoff value of 2.0, and 33 cases (26.0%) had an LMR ≤2.0. Cases with LMR ≤2.0 had a significantly earlier progression than those with LMR > 2.0, based on the TTNT (P = .0007). Additionally, LMR ≤2.0 indicates earlier progression in TTNT when comparing only FL and low-grade B-cell lymphoma cases without FL (P = .007, 0.002). For multivariate analysis, the factors associated with an LMR ≤2.0 (HR, 2.741; 95% CI, 1.4330-5.245; P = .002) were considered as early progression factors with regard to the TTNT. CONCLUSION: Lymphocyte-monocyte ratio effectively predicts the efficacy of bendamustine therapy for low-grade B-cell lymphoma, particularly FL; its application may improve treatment strategies for this disease.


Assuntos
Cloridrato de Bendamustina/administração & dosagem , Linfócitos , Linfoma de Células B , Linfoma Folicular , Monócitos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Linfócitos/patologia , Linfoma de Células B/sangue , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma Folicular/sangue , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/patologia , Recidiva , Estudos Retrospectivos
18.
Cancer Immunol Immunother ; 69(6): 913-925, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32322910

RESUMO

Follicular lymphoma (FL) is a remarkably immune-responsive malignancy, which is still considered incurable. As, standard immunochemotherapy is complex, toxic and not curative, improvement in FL care is now a crucial topic in hemato-oncology. Recently, we and others have shown that dendritic cell (DC)-based therapies allow a specific immune response associated with sustained lymphoma regression in a proportion of low-tumor burden FL patients. Importantly, the rate of objective clinical response (33-50%) and of sustained remission is remarkably higher compared to similar studies in solid tumors, corroborating the assumption of the immune responsiveness of FL. Our experimental intra-tumoral strategy combined injection with rituximab and interferon-α-derived dendritic cells (IFN-DC), a novel DC population particularly efficient in biasing T-helper response toward the Th1 type and in the cross-priming of CD8 + T cells. Noteworthy, intra-tumoral injection of DC is a new therapeutic option based on the assumption that following the induction of cancer-cell immunogenic death, unloaded DC would phagocytize in vivo the tumor associated antigens and give rise to a specific immune response. This approach allows the design of easy and inexpensive schedules. On the other hand, advanced and straightforward methods to produce clinical-grade antigenic formulations are currently under development. Both unloaded DC strategies and DC-vaccines are suited for combination with radiotherapy, immune checkpoint inhibitors, immunomodulators and metronomic chemotherapy. In fact, studies in animal models have already shown impressive results, while early-phase combination trials are ongoing. Here, we summarize the recent advances and the future perspectives of DC-based therapies in the treatment of FL patients.


Assuntos
Células Dendríticas/imunologia , Imunoterapia/métodos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/imunologia , Humanos , Linfoma Folicular/patologia
19.
Diagn Pathol ; 15(1): 31, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245492

RESUMO

BACKGROUND: Reverse Variant of Follicular Lymphoma (RVFL) is one of the rare morphological variants of FL, characterized by dark staining small centrocytes in the center and pale staining large centroblasts at the periphery of the neoplastic follicles. Only rare cases of RVFL have been described to date. The histological appearance of this little known variant of FL may be misinterpreted if pathologists are unaware of its existence. The main purpose of this study is to draw pathologists' attention to such an uncommon growth pattern of FL so that this variant can be correctly recognized and the clinical significance further studied in the future. METHODS: Four cases of FL with unusual morphologic features were evaluated for the expression pattern of CD20, CD10, BCL6, BCL2, CD21, CD23, CD3, CD5, Cyclin D1, IgD and Ki67 by immunohistochemistry. Fluorescence in situ hybridization (FISH) with break-apart probes was performed to detect BCL2 gene rearrangement. RESULTS: All four cases showed distinctive morphologic pattern of RVFL; in addition, each also exemplified unique morphological features. Immunohistochemical stains confirmed the cells in both the central areas and the peripheral cuffs had the same immunophenotypic profiles, contrasting to the FL with marginal zone differentiation in which only the center of the nodules showed expression of CD10. FISH demonstrated BCL2 gene rearrangement in all cases. CONCLUSION: The growth pattern of this rare FL variant may mimic FL with marginal-zone differentiation and other entities including but not limited to marginal zone lymphoma (MZL), progressive transformation of germinal centers (PTGC) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Pathologists should be familiar with this unusual morphological variant to avoid diagnostic pitfalls.


Assuntos
Linfonodos/patologia , Linfoma Folicular/patologia , Adulto , Biomarcadores Tumorais/análise , Feminino , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Folicular/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA