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1.
Int J Cancer ; 150(2): 327-334, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34520566

RESUMO

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with Epstein-Barr encoding region (EBER) status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cutoff points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV DNA in natural killer T-cell lymphoma (NKTL) patients was higher than that in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and peripheral T-cell lymphoma, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the combination of EBV and EBER status could differentiate the prognosis of HL.


Assuntos
DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Doença de Hodgkin/diagnóstico , Linfoma Folicular/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma de Células T/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Viral/análise , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/virologia , Humanos , Linfoma Folicular/epidemiologia , Linfoma Folicular/virologia , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/virologia , Linfoma de Células T/epidemiologia , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
2.
Clin Nucl Med ; 47(1): 81-82, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34172596

RESUMO

ABSTRACT: We herein report a case involving a 67-year-old man with concomitant progressive follicular lymphoma and gastric carcinoma. Baseline 18F-FDG PET/CT showed high metabolic activity in multiple nodal stations and a thickened gastric antrum wall, whereas 68Ga-FAPI-04 PET/CT depicted very intense tracer uptake in the gastric lesion but mild uptake in the nodes. After the treatment, complete remission from lymphadenopathy was achieved, whereas the gastric lesion accumulated more radiotracers compared with baseline levels. Despite our incorrect initial assumption of B-cell transformation, molecular imaging was able to profile the characteristics of these 2 diseases.


Assuntos
Carcinoma , Linfoma Folicular , Idoso , Fluordesoxiglucose F18 , Humanos , Linfoma Folicular/diagnóstico por imagem , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Quinolinas
3.
Clin Nucl Med ; 47(1): e47-e48, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34319949

RESUMO

ABSTRACT: Prostate-specific membrane antigen (PSMA) PET/CT is a highly reliable nuclear tracer for diagnostic imaging of prostate cancer. However, PSMA is also expressed by some nonprostatic tissues such as benign tumors, inflammatory processes, and malignant neoplasms. This case presents a patient with prostate cancer and follicular lymphoma undergoing PSMA PET/CT. Remarkably, both tumor entities were clearly detected in the scan. Yet, the 2 malignancies demonstrated rather different ranges in terms of SUVmax uptake values and therefore still enabled precise and accurate discrimination of prostate cancer and follicular lymphoma.


Assuntos
Linfoma Folicular , Neoplasias da Próstata , Ácido Edético , Humanos , Linfoma Folicular/diagnóstico por imagem , Masculino , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem
4.
Ann Clin Microbiol Antimicrob ; 20(1): 85, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34969393

RESUMO

BACKGROUND: There is growing evidence that antibody responses play a role in the resolution of SARS-CoV-2 infection. Patients with primary or secondary antibody deficiency are at increased risk of persistent infection. This challenging clinical scenario is associated with adverse patient outcome and potentially creates an ecological niche for the evolution of novel SARS-CoV-2 variants with immune evasion capacity. Case reports and/or series have implied a therapeutic role for convalescent plasma (CP) to secure virological clearance, although concerns have been raised about the effectiveness of CP and its potential to drive viral evolution, and it has largely been withdrawn from clinical use in the UK. CASE PRESENTATION: We report two cases in which persistent SARS-CoV-2 infection was cleared following administration of the monoclonal antibody combination casirivimab and imdevimab (REGN-COV2, Ronapreve). A 55-year-old male with follicular lymphoma, treated with B cell depleting therapy, developed SARS-CoV-2 infection in September 2020 which then persisted for over 200 days. He was hospitalised on four occasions with COVID-19 and suffered debilitating fatigue and malaise throughout. There was no clinical response to antiviral therapy with remdesivir or CP, and SARS-CoV-2 was consistently detected in nasopharyngeal swabs. Intrahost evolution of several spike variants of uncertain significance was identified by viral sequence analysis. Delivery of REGN-COV2, in combination with remdesivir, was associated with clinical improvement and viral clearance within 6 days, which was sustained for over 150 days despite immunotherapy for relapsed follicular lymphoma. The second case, a 68-year-old female with chronic lymphocytic leukaemia on ibrutinib, also developed persistent SARS-CoV-2 infection. Despite a lack of response to remdesivir, infection promptly cleared following REGN-COV2 in combination with remdesivir, accompanied by resolution of inflammation and full clinical recovery that has been maintained for over 290 days. CONCLUSIONS: These cases highlight the potential benefit of REGN-COV2 as therapy for persistent SARS-CoV-2 infection in antibody deficient individuals, including after failure of CP treatment. Formal clinical studies are warranted to assess the effectiveness of REGN-COV2 in antibody-deficient patients, especially in light of the emergence of variants of concern, such as Omicron, that appear to evade REGN-COV2 neutralisation.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , /virologia , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes , COVID-19/terapia , Combinação de Medicamentos , Feminino , Humanos , Imunização Passiva , Linfoma Folicular , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Resultado do Tratamento
5.
Bull Cancer ; 108(10S): S28-S39, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34920805

RESUMO

Three CD19 CAR-T cells (Yescarta®, Kymriah® and Breyanzi®), have been approved in relapsed or refractory diffuse large B cell lymphomas (DLBCL) after at least two previous lines of therapy. These immunotherapies have transformed the prognosis of these lymphomas, which can't be cured by conventional treatments. Long-term updates of registration studies as well as the first real-life data allow a better knowledge of the efficacy of these emerging therapies, their toxicity and their resistance mechanisms. These advances have also led to consider the earlier use of CAR-T cells in the therapeutic strategy and to extend it to other B lymphomas such as mantle cell and indolent lymphomas. Indeed, Yescarta® and Tecartus® have been recently approved in those malignancies, Furthermore, other strategies are being investigated to develop new CAR-T cells to target Hodgkin's lymphomas and T-cell lymphomas, although data in these settings still have to be completed. In this article, we review the latest data on the use of CAR-T cells in lymphomas.


Assuntos
Imunoterapia Adotiva/métodos , Linfoma/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/transplante , Antígenos CD19/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Doença de Hodgkin/imunologia , Doença de Hodgkin/terapia , Humanos , Imunoterapia Adotiva/efeitos adversos , Depleção Linfocítica/métodos , Linfoma/imunologia , Linfoma Folicular/imunologia , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/terapia , Linfoma de Célula do Manto/imunologia , Linfoma de Célula do Manto/terapia , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/terapia , Linfoma de Células T Periférico/imunologia , Linfoma de Células T Periférico/terapia , Receptores de Antígenos de Linfócitos T/uso terapêutico , Linfócitos T/imunologia
6.
Bull Cancer ; 108(10S): S4-S17, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34920806

RESUMO

Chimeric antigen receptors (CAR)-T cells are genetically engineered T-lymphocytes redirected with a predefined specificity to any target antigen, in a non-HLA restricted manner, therefore combining antibody-type specificity with effector T-cell function. This strategy was developed some thirty years ago, after extensive work established the key role of the immune system against cancer. The first-engineered T-cell with chimeric molecule was designed in 1993 by Israeli immunologist Zelig Eshhar. Since then, several modifications took place, including the addition of co-stimulatory domain, to further improve CAR-T cell anti-tumor potency. The first clinical application of CAR-T cell was done in Rotterdam in 2005 for metastatic renal cell carcinoma and simultaneously at the National Cancer Institute (NCI) for metastatic ovarian cancer. These pioneered studies failed to demonstrate a therapeutic benefit, but warning emerged concerning their safety of use. The real clinical success came with anti-CD19 CAR-T cells, used since 2009 by Steven Rosenberg at the NCI in a patient with refractory follicular lymphoma and in 2011 by Carl June and David Porter from the University of Pennsylvania in patients with chronic lymphocytic leukemia and B-cell acute lymphoblastic leukemia. From that time, large centers in North America have embarked in several early phase and pivotal trials that have demonstrated unprecedent response rate in heavily pretreated chemo refractory patient with B-cell malignancies. Theses clinical success have led to the approval of three anti-CD19 CAR-T cells products for the management of B-cell malignancies in the United States and in Europe as of December 2020.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/transplante , Especificidade de Anticorpos , Antígenos CD19/imunologia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Ensaios Clínicos como Assunto , Europa (Continente) , Feminino , História do Século XVIII , História do Século XIX , História do Século XX , Humanos , Imunoterapia Adotiva/história , Israel , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Leucemia Linfocítica Crônica de Células B/terapia , Depleção Linfocítica/métodos , Linfócitos do Interstício Tumoral/transplante , Linfoma Folicular/terapia , Mieloma Múltiplo/terapia , Neoplasias/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/imunologia , Estados Unidos
7.
Am J Case Rep ; 22: e931772, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34764233

RESUMO

BACKGROUND The incidence of multiple primaries in cancer patients is 2-17%. However, the synchronous co-occurrence of adenocarcinoma of the breast and follicular lymphoma is rare. CASE REPORT We describe a case series of 3 post-menopausal women who presented to our institute with a breast lump. On further investigations, 2 of them had invasive ductal carcinoma and 1 had invasive lobular carcinoma of the breast. All 3 cancers were estrogen/progesterone receptor (ER/PR)-positive and human epidermal growth factor receptor 2 (HER-2)-negative. During the staging PET scans, all 3 patients had increased FDG uptake in axillary, mesenteric, and inguinal lymph nodes, respectively, raising concerns for metastatic disease. However, subsequent biopsies revealed them as follicular lymphomas occurring as a second concurrent primary malignancy. All patients underwent radical mastectomies with sentinel lymph node dissection followed by chemotherapy and hormonal therapy. Most of the lymphomas were low grade, which the oncologist closely followed. CONCLUSIONS Very few cases of breast cancer and follicular lymphoma co-occur; this is not limited to the axillary lymph nodes and can occur in any part of the lymphatic chain. Regional lymph node enlargement detected on examination or imaging does not always indicate metastasis. A high index of suspicion is needed followed by lymph node biopsy to rule out any second primary malignancy.


Assuntos
Neoplasias da Mama , Linfoma Folicular , Axila , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática , Linfoma Folicular/diagnóstico , Biópsia de Linfonodo Sentinela
8.
Gan To Kagaku Ryoho ; 48(11): 1369-1373, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34795129

RESUMO

BACKGROUND: Obinutuzumab is used to treat follicular lymphoma in Japan. Its characteristic adverse event is infusion- related reactions(IRRs). Although interruption of administration improves many IRRs, serious symptoms can occur; thus, timing the interruption to correspond with the onset of these symptoms is necessary. However, the specific symptoms and timing of IRRs caused by obinutuzumab remain unclear. Therefore, the purpose of this study was to clarify the specific symptoms and timing of the onset of IRRs with obinutuzumab treatment. METHODS: Thirty patients were administered obinutuzumab for one year from October 2018 to September 2019. The frequency of IRRs, expression time, severity, symptoms, and correspondence were investigated. RESULTS: IRRs occurred in 13 patients(43.3%), and all occurred after the first dosing. In 9 of 13 cases(69.2%), IRRs occurred within 90 min of the first dosage. Grade 3 symptoms were expressed in 1 of 13 cases (7.7%). The symptoms of IRRs were throat discomfort, breathing difficulty, skin rash, chills, and fever. CONCLUSIONS: Most IRRs due to obinutuzumab occurred within 90 min of the first dosage. They were mostly Grade 2 or lower, and the frequency of serious IRRs was low. Thus, careful observation of symptoms during treatment with obinutuzumab is necessary.


Assuntos
Linfoma Folicular , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Japão , Linfoma Folicular/tratamento farmacológico
10.
Medicine (Baltimore) ; 100(43): e27610, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713841

RESUMO

INTRODUCTION: Endoscopic resection of a follicular lymphoma (FL) presenting as a gastric subepithelial tumor (SET), along with periodic follow up can be a treatment option because gastrointestinal FL cells tend to reside in the primary site, which may explain its indolent nature. PATIENT CONCERNS: A gastric lesion was found incidentally during a screening endoscopy in 73-year-old woman without any gastrointestinal symptom. DIAGNOSIS: The patient was diagnosed with a grade I FL that was 1.4 cm large, at the greater curvature of lower-body. INTERVENTION: We performed underwater endoscopic mucosal resection (UW-EMR), and there was no serious complication, such as bleeding and perforation. OUTCOMES: Complete en bloc resection was achieved with UW-EMR. Follow-up endoscopic biopsy after 3 months revealed no residual tumor on the resection site. CONCLUSION: UW-EMR may be a simple and safe resection method for gastric FL without metastases, that measure >1 cm.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Neoplasias Gastrointestinais/cirurgia , Linfoma Folicular/cirurgia , Água , Idoso , Feminino , Neoplasias Gastrointestinais/patologia , Humanos , Linfoma Folicular/patologia
11.
Rinsho Ketsueki ; 62(8): 1070-1076, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497193

RESUMO

The prognosis of patients with follicular lymphoma (FL) has improved over the last decades. However, most patients with FL will eventually relapse. The management of FL is mainly determined by clinical stage and tumor burden. For localized-stage patients, an involved-field radiation therapy is recommended. For advanced-stage low tumor burden patients, watchful waiting remains the standard treatment, whereas rituximab monotherapy may be an alternative option. Immuno-chemotherapy combined with rituximab maintenance has been the standard care for patients with high tumor burden. Recently, the novel anti-CD20 monoclonal antibody obinutuzumab was approved for the treatment of FL. Obinutuzumab with chemotherapy followed by obinutuzumab maintenance is considered one of the standard therapeutic options. After relapse or progression, it is necessary to consider a treatment strategy based on several disease-related, treatment-related, and patient-related factors. During the last decade, the development of biological knowledge and use of molecularly targeted agents offer new therapeutic perspectives with chemo-free strategies. This review highlights the current standards for the treatment of FL.


Assuntos
Antineoplásicos , Linfoma Folicular , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Linfoma Folicular/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab/uso terapêutico
13.
Blood Adv ; 5(20): 4303-4312, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34570196

RESUMO

The survival and proliferation of follicular lymphoma (FL) cells are strongly dependent on macrophages, because their presence is necessary for the propagation of FL cells in vitro. To this regard, as also shown for the majority of solid tumors, a high tissue content of tumor-associated macrophages (TAMs), particularly if showing a protumoral phenotype (also called M2), is strongly associated with a poor outcome among patients with FL treated with chemotherapy. The introduction of rituximab, an anti-CD20 antibody that can be used by TAMs to facilitate antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, has challenged this paradigm. In the rituximab era, clinical studies have yielded conflicting results in FL, showing variable outcomes based on the type of regimen used. This highlighted, for the first time, that the impact of TAMs on the prognosis of patients with FL may depend on the administered treatment, emphasizing the need to better understand how currently available therapies affect macrophage function in FL. We summarize the impact of approved and novel therapies for FL, including radiation therapy, chemotherapy, anti-CD20 monoclonal antibodies, lenalidomide, and targeted agents, on the biology of TAMs and describe their effects on macrophage phagocytosis, polarization, and function. Although novel agents targeting the CD47/SIRPα axis are being developed and show promising activity in FL, a deeper understanding of macrophage biology and their complex pathways will help to develop novel and safer therapeutic strategies for patients with this type of lymphoma.


Assuntos
Antineoplásicos , Linfoma Folicular , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Humanos , Linfoma Folicular/tratamento farmacológico , Macrófagos , Rituximab/uso terapêutico
14.
J Transl Med ; 19(1): 399, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544443

RESUMO

BACKGROUND: This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. METHOD: RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. RESULTS: A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan-Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25-0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. CONCLUSION: CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.


Assuntos
Linfoma Folicular , Quimiocina CCL19 , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Prognóstico , Intervalo Livre de Progressão
15.
Blood Adv ; 5(20): 4185-4197, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34529789

RESUMO

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions. We present the largest single-institution VLDRT experience of adult patients with follicular lymphoma or marginal zone lymphoma treated between 2005 and 2018 (299 lesions; 250 patients) using modern principles including positron emission tomography staging and involved site radiotherapy. Outcomes include best clinical or radiographic response between 1.5 and 6 months after VLDRT and cumulative incidence of local progression (LP) with death as the only competing risk. After VLDRT, the overall response rate was 90% for all treated sites, with 68% achieving complete response (CR). With a median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after first-line treatment with VLDRT for potentially curable, localized disease. Lesion size >6 cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive involved site radiotherapy strategy in which patients will be treated initially with VLDRT, reserving full-dose treatment for those who are unable to attain a CR.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Humanos , Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma Folicular/radioterapia , Cuidados Paliativos , Dosagem Radioterapêutica , Indução de Remissão
16.
Blood Adv ; 5(17): 3354-3361, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477816

RESUMO

Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks). Primary end points were previously reported, proving noninferiority of efficacy and pharmacokinetic equivalence of CT-P10 to rituximab. Secondary end points included overall response rate (PR+CR) during the induction period per 2007 International Working Group (IWG) criteria, survival analyses, and overall safety. Between 28 July 2014 and 29 December 2015, 140 patients were randomized (70 per group). Median follow-up was 39.9 months (interquartile range, 36.7-43.5). Per 1999 IWG criteria, 4-year Kaplan-Meier estimates (95% confidence interval [CI]) for CT-P10 and rituximab were 61% (47% to 73%) and 55% (36% to 70%) for progression-free survival (hazard ratio, 1.33 [95% CI, 0.67-2.63]; P=.409), respectively, and 88% (77% to 94%) and 93% (83% to 97%) for overall survival (5.29 [0.84-33.53]; P=.077). Overall, 90% (CT-P10) and 86% (rituximab) of patients experienced treatment-emergent adverse events. Long-term safety profiles were similar between groups. Findings confirm favorable outcomes for CT-P10-treated patients with advanced-stage FL and demonstrate comparable long-term efficacy and overall safety between CT-P10 and rituximab. This trial was registered at www.clinicaltrials.gov as #NCT02162771.


Assuntos
Medicamentos Biossimilares , Linfoma Folicular , Anticorpos Monoclonais Murinos , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Rituximab/efeitos adversos
17.
Eur J Cancer ; 157: 132-139, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34508995

RESUMO

BACKGROUND: Primary refractory (PREF) follicular lymphoma (FL) has a completely different clinical course from that of FL that responds to front-line treatments. In addition to having poor responses to salvage therapies, it seems that patients with PREF are at increased risk of histological transformation (HT). The Aristotle consortium presented the opportunity of investigating the risk of HT in a very large series of cases. Thus, we investigated the risk of HT in patients with PREF FL compared with that of responding patients or in stable disease and ultimately their outcome. METHODS: Six thousand three hundred thirty-nine patients from the Aristotle database were included in the analysis. These patients had a histologically confirmed grade 1, 2 or 3a FL diagnosed between 1997 and 2013. The primary end-points were the cumulative incidence (CI) of HT at the first progression or relapse and the survival after transformation. FINDINGS: The 5-year CI of HT among patients with PREF was 34% (95% confidence interval (CI): 27-43), whilst it was 7.1% (95% CI: 6.0-8.5) in the group of patients with partial response (PR) or stable disease (SD) (PR + SD) and 3.5% (95% CI: 3.0-4.2) in the group of patients achieving complete response (CR). The 5-year survival after relapse (SAR) was 33% (95% CI: 28-39) for the PREF group, 57% (95% CI 54-61) in patients with PR, 51% (95% CI 43-58) in the SD group after first-line therapy and 63% (95% CI: 66-72) in patients with CR after initial treatment (p-value <0.001). The 5-year SAR for those patients with PREF who developed HT was 21% (95% CI: 12-31), clearly diminished when compared with those patients with PREF who did not experience HT (38% [95% CI: 31-44]) (p-value = 0.001). INTERPRETATION: Patients with PREF FL have a dismal outcome and an associated very high rate of HT that further worsens their poor prognosis.


Assuntos
Linfoma de Células B/patologia , Linfoma Folicular/patologia , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Sci Rep ; 11(1): 18496, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531504

RESUMO

Despite follicular lymphoma (FL) is frequently characterized by a moderate increase of glucose metabolism, PET/CT examinations provides valuable information for staging and response assessment of the disease. The aim of the study was to assess and compare the diagnostic performance of PET/ldCT and PET/ceCT, respectively, in evaluating FL patients at the end of treatment. Fifty FL consecutive patients who underwent end-of-therapy PET/CT with both ldCT and ceCT were analyzed. Two blinded observers independently assessed PET/ldCT and PET/ceCT applying the Deauville score (DS) and Lugano classification criteria. PET imaging obtained after the end-of-treatment (EoT) was classified as showing PET and ce-CT matched response (concordant imaging group, CIG) or PET and ce-CT unmatched response (discordant imaging group, DIG). Relapse rate and Event-Free Survival (EFS) were compared between CIG and DIG patients. Overall, no differences in metabolic response classification were observed between PET/ldCT and PET/ceCT. In 13 (26%) patients PET/ceCT identified additional FDG-negative nodal lesions in mesenteric, retroperitoneal and iliac regions. However, in all cases, final DS remained unchanged and the additional results did not modify the following therapeutic decision. Among patients, who obtained complete metabolic response a comparable rate of relapse was registered in DIG 3/13 (23%) and CIG subgroups 5/20 (25%) [p = 0.899]. In all 3 DIG cohort patients who relapsed the recurrent disease involved also, but not exclusively, PET negative lymph nodes detected by ceCT. In overall population metabolic response defined by PET/ldCT predicted EFS [76% (group of patients with metabolic response) vs 35% (group of patients with residual disease), p = 0.0013] significantly better than ceCT-Based response assessment [75% (group of patients with complete response) vs 53% (group of patients with residual disease), p = 0.06]. Our study demonstrates a negligible diagnostic and predictive value of ceCT performed in addition to standard 18FDG PET/ldCT for EoT response evaluation in FLs. PET/ldCT should be performed as first-line imaging procedure, also in patients with prevalent abdominal and pelvic involvement, limiting the acquisition of ceCT in selected cases. This tailored approach would contribute to avoid useless radiation exposure and preserve renal function of patients.


Assuntos
Abdome/diagnóstico por imagem , Linfoma Folicular/diagnóstico por imagem , Pelve/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Taxa de Sobrevida
19.
In Vivo ; 35(5): 2785-2791, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410969

RESUMO

BACKGROUND/AIM: Malignant lymphoma (ML) cases with overlapping gastrointestinal (GI) lesions are often encountered. We aimed to elucidate the importance of examining the GI tract in patients with ML and assess the overlap rate. PATIENTS AND METHODS: We analysed 190 patients diagnosed with GI MLs. We compared the overlap rates among the different histopathological types. RESULTS: Twenty-five (13.2%) patients had overlapping GI lesions in more than two segments. The overlap rates were 100% in mantle cell lymphomas (MCL), 27.6% in follicular lymphomas (FL), and 16.3% in diffuse large B-cell lymphomas (DLBCL). MCL, FL, and DLBCL cases showed significantly higher overlap rates than mucosa-associated lymphoid tissue lymphoma cases (p<0.01). About 64.0% of cases of ML with overlapping lesions involved the small intestine. CONCLUSION: In GI ML cases, it is ideal to examine the entire GI tract by esophagogastroduodenoscopy, colonoscopy, and capsule endoscopy and/or balloon-assisted endoscopy, especially in MCL, FL, and DLBCL.


Assuntos
Neoplasias Gastrointestinais , Linfoma Folicular , Linfoma Difuso de Grandes Células B , Adulto , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia
20.
Acta Oncol ; 60(10): 1361-1368, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34346830

RESUMO

Introduction: Primary cutaneous indolent B-cell lymphomas (PCBCLs) are not well characterized due to their rarity and indolent character.Methods: We retrospectively reviewed the data from 52 patients with primary cutaneous follicular lymphoma (PCFL) (n = 26), marginal zone lymphoma (PCMZL) (n = 25) or undefined PCBCL (n = 1) treated in 10 hematology centers in 1999-2019.Results: Patients characteristics and diagnostic approach: In almost half of the patients, pruritus or pain were present at diagnosis. The lesions were predominantly located on the head and trunk. The disease was present in a form of solitary infiltration or disseminated lesions with a similar frequency.Treatment details and outcomes: Surgery, radiotherapy, rituximab alone or combined with chemotherapy were applied as first-line treatment in 33%, 25%, 21% and 21% of patients, with complete response (CR) achieved by 94%, 83%, 50% and 70% of patients, respectively (p = 0.28). The median duration of response (DoR) was 65 months (95%CI 35-155).Survival: After the median follow-up time of 46 months (range: 3-225), the estimated 5-year overall survival (OS) and progression-free survival (PFS) were 93% and 54%, respectively.Discussion: Clinical presentation was largely consistent with the literature data, however, we observed some differences, including higher predilection to affect upper extremities (25%) and more frequent multifocal appearance in PCFCL (64%) and unifocal in PCMZL (70%).A high proportion of patients with indolent PCBCL achieved CR after the first-line therapy (77%), regardless of treatment mode. We did not find any impact of clinical features on treatment outcomes.Conclusions: All treatment modalities resulted in a high overall response rate. Surgery and/or radiotherapy are the optimal therapeutic options for patients with localized disease. The decision to treat systemically should rather be limited to the generalized form of the disease. High response rate, long duration of remission and excellent long-term survival confirm the truly indolent character of PCFCL and PCMZL.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Neoplasias Cutâneas , Humanos , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma Folicular/terapia , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , Rituximab , Neoplasias Cutâneas/terapia
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