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1.
Medicine (Baltimore) ; 99(40): e22408, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019417

RESUMO

The epidemiology of lymphomas has changed since the use of antiretroviral therapy. The incidence of Non-Hodgkin Lymphomas (NHL) has significantly decreased in high income countries but not in low and middle-income countries where AIDS-related events remain high. This observational study describes the characteristics, infectious complications and main outcomes of patients diagnosed with HIV and lymphoma at the Instituto Nacional de Cancerología.All adults >18 years diagnosed with HIV and lymphoma from January 2010 to December 2017 were included. Information on HIV and lymphoma was collected, as well as the occurrence of co-infections at diagnosis and during therapy. Multiple regression was done with NHL patients to evaluate independent variables associated to death.One hundred fifty three patients were included: 127 patients with NHL (83%) and 26 (17%) with Hodgkin lymphoma (HL). Of the NHL, 49 (38%) were diffuse large B cell Lymphomas (DLBCL), 35 (27%) plasmablastic, 28 (23%) Burkitt, 10 (8%) primary DLBCL of Central Nervous system, 3 (2%) T-cell lymphomas, and 2 (2%) pleural effusion lymphoma. Most patients were diagnosed in an advanced stage: 70% of NHL had a high International Prognostic Index (IPI); 68% of patients had <200 cells/mm. Almost 25% of NHL patients had an opportunistic infection at lymphoma diagnosis. During chemotherapy, 60% of all patients presented with at least 1 serious non-opportunistic infectious complication, and 50% presented 2 or more infectious complications, mostly bacterial infections. Thirty six percent of NHL and 23% of HL died. After adjusting for confounders, the variables associated with death were IPI and lymphoma type.HIV positive patients with lymphoma in our institution are diagnosed with an advanced stage and a high burden of infections complications. Death remains high and the variables strongly associated with death are those related to lymphoma prognosis such as lymphoma type and IPI.


Assuntos
Infecções por HIV/epidemiologia , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Infecções Oportunistas/epidemiologia , Adulto , Feminino , Infecções por HIV/patologia , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Infecções Oportunistas/microbiologia , Estudos Retrospectivos
2.
Int Heart J ; 61(5): 1041-1043, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32879262

RESUMO

The current treatment of radiation-induced coronary artery disease (RCAD) is comparable to that of generic coronary artery disease (CAD); however, the outcomes of these treatment measures have not been fully examined in RCAD. A 33-year-old woman, without conventional cardiovascular risk factors, presented with left main coronary artery (LMCA) lesions. At the age of 26, she received mediastinal radiation therapy (RT) to treat mixed cellularity Hodgkin lymphoma. One BiodivYsio 3.5 × 18 mm stent was implanted at the LMCA site. At the age of 38, the patient was treated by balloon dilatation because of approximately 50% in-stent stenosis. At the last follow-up in February 2018, when the patient was 51 years old, she no longer complained of chest pain. Coronary angiography showed no de novo or in-stenosis lesions, although optical coherence tomography showed mild neointimal proliferation, calcific plaque, small ruptured intima, and several uncovered struts. The experience of treating this case may shed some light on coronary stenting in coronary lesions caused by RCAD.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana/terapia , Reestenose Coronária/terapia , Doença de Hodgkin/radioterapia , Lesões por Radiação/terapia , Stents , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mediastino , Pessoa de Meia-Idade , Neointima/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Tomografia de Coerência Óptica
3.
Rinsho Ketsueki ; 61(8): 890-900, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908053

RESUMO

Although Hodgkin lymphoma is now among the most curable of the lymphomas, the relapse rate after the first-line treatment remains at 20-30%. Brentuximab vedotin (BV) has been developed for the treatment of newly diagnosed classical Hodgkin lymphoma (cHL), relapsed/refractory cHL, or consolidation after autologous stem cell transplantation. Notably, BV treatment combined with doxorubicin, vinblastine, and dacarbazine treatment has been established as standard treatment for newly diagnosed advanced-stage cHL. Immune-checkpoint inhibitors represent another class of promising cancer immunotherapies that may be used to treat advanced cancers, including cHL. Anti-programmed death-1-blocking antibodies have been used to enhance immunity in cases of several malignancies and obtain durable responses, most notably in patients who have been administered heavy treatment for relapsed/refractory cHL. Several clinical trials, including single agents or combination therapies for cHL, have been developed or are currently under investigation. The results of the ongoing and future clinical trials may establish new paradigms for the treatment of cHL.


Assuntos
Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Humanos , Imunoconjugados , Recidiva Local de Neoplasia , Transplante Autólogo
4.
Anticancer Res ; 40(9): 4907-4912, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878778

RESUMO

BACKGROUND/AIM: We investigated the effects of luteolin (LUT) on classical Hodgkin's lymphoma (cHL), since such studies in malignant lymphomas are lacking. MATERIALS AND METHODS: Effect of LUT on cell growth was assessed with water-soluble tetrazolium 1 (WST-1) cell proliferation assay and automated hemocytometry on trypan blue-exclusion assay. Cell death was investigated with acridine orange/ethidium bromide live-dead assay, propidium iodide (PI) flow cytometry, and Annexin-V-PI microscopy. Caspase activation was studied using CellEvent Caspase-3/7 Green detection reagent. High resolution immunofluorescence microscopy was used to detect cleaved-PARP-1. RESULTS: LUT induced a dose-dependent decrease in the growth of KMH2 and L428 cells, cellular models of mix-cellularity (MC) and nodular sclerosis (NS) cHL, respectively. However, LUT induced cell death only in KMH2, at a higher concentration, and this was associated with caspase activation and cleaved PARP-1. CONCLUSION: LUT induces cytotoxicity in the MC-cHL cellular model KMH2 via caspase activation.


Assuntos
Antineoplásicos/farmacologia , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Luteolina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Poli(ADP-Ribose) Polimerase-1/metabolismo
5.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 649-654, 2020 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-32942818

RESUMO

Objective: To summarize the efficiency and long-term outcomes of limited-stage Hodgkin lymphoma in children and adolescents with ABVD therapy and determined whether omitting radiotherapy for a low-risk patient enabled the achievement of complete response (CR) after chemotherapy. Methods: We retrospectively analyzed data from 13 y (2004-2016) from patients aged ≤18 y with limited-stage HL admitted to the Sun Yat-sen University Cancer Center. Patients received treatment with ABVD chemotherapy alone or ABVD chemotherapy followed by low-dose involved field radiotherapy. Results: Total 85 subjects were eligible for study inclusion; the median age was 12 (3-18) y; 66 (77.6%) were men, 80 (94.1%) had stage-II disease, 56 (65.9%) were at low-risk, and the median follow-up duration was 72 (8-196) months; 12 relapsed, 2 had secondary neoplasm, and 2 died. The 5-year event free survival (EFS) was (85.6±3.8) %, and the overall survival (OS) was 100%. The 5-year EFS and OS was (89.1±4.2) % and 100%, respectively, for the low-risk cohort and (79.3±7.5) % and 100%, respectively for the intermediate-risk cohort. Among the 39 low-risk patients who achieved CR after chemotherapy, 15 received treatment with chemotherapy followed by LD-IFRT. In the exploratory subset analysis, the low-risk cohort who achieved CR after chemotherapy, the 5-year EFS for comparing ABVD alone with chemotherapy followed by LD-IFRT was (87.0±7.0) % versus 100% (P=0.506) , and the OS was 100% for both the groups. Conclusions: Our retrospective analysis showed excellent survival of limited-stage HL patients with ABVD therapy. For patients who achieving CR after chemotherapy with low-risk HL, received chemotherapy followed by LD-IFRT does not improve 5-year OS and EFS. The use of risk- and response-based stratification may facilitate the development of effective and less toxic protocols.


Assuntos
Doença de Hodgkin , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Criança , Pré-Escolar , Dacarbazina , Intervalo Livre de Doença , Doxorrubicina , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Vimblastina
6.
Lancet Haematol ; 7(9): e660-e670, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32853585

RESUMO

BACKGROUND: Recognising that the immune suppressive microenvironment promotes tumour growth in Hodgkin lymphoma, we hypothesised that activating immunity might augment the activity of targeted chemotherapy. We evaluated the safety and activity of combinations of brentuximab vedotin with nivolumab or ipilimumab, or both in patients with relapsed or refractory Hodgkin lymphoma. METHODS: In this multicentre, open-label, phase 1/2 trial, patients with relapsed or refractory Hodgkin lymphoma aged 18 years or older who had relapsed after at least one line of therapy, with an Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ and marrow function, with no pulmonary dysfunction were eligible for inclusion. Phase 1 primary objectives were to determine the maximum tolerated dose and dose limiting toxicities of brentuximab vedotin combined with ipilimumab (ipilimumab group), nivolumab (nivolumab group), or both (triplet therapy group) using a 3 + 3 dose escalation design with expansion cohorts. During the dose escalation phase, patients were enrolled sequentially into one of six cohorts: in the ipilimumab group fixed brentuximab vedotin 1·8 mg/kg with ipilimumab 1 mg/kg (cohort A) or 3 mg/kg (cohort B); in the nivolumab group fixed nivolumab 3 mg/kg with brentuximab vedotin 1·2 mg/kg (cohort D) or 1·8 mg/kg (cohort E); and in the triplet therapy group fixed nivolumab 3 mg/kg and ipilimumab 1 mg/kg with brentuximab vedotin 1·2 mg/kg (cohort G) or 1·8 mg/kg (cohort H). Additional patients were enrolled in the expansion phase at the same doses of cohorts B, E, and H. All drugs were given intravenously; brentuximab vedotin and nivolumab were given every 3 weeks, ipilimumab was given every 6 weeks in the ipilimumab group and every 12 weeks in the triplet therapy group. All eligible and treated patients were included in the analysis. This phase 1/2 study is registered with ClinicalTrials.gov, NCT01896999. The phase 2, randomised portion of the trial is still enrolling. FINDINGS: Between March 7, 2014, and Dec 28, 2017, 64 patients were enrolled; two patients in the ipilimumab group and one patient in the nivolumab group were excluded due to ineligibility after enrolment and 61 were evaluable. A total of six dose limiting toxicities were reported in four patients, and the doses used in cohorts B, E, and H were established as maximum tolerated doses and patients were subsequently enrolled onto expansion cohorts (C, F, and I) with these schedules. There were ten (43%) grade 3-4 treatment related adverse events in the ipilimumab group, three (16%) in the nivolumab group, and 11 (50%) in the triplet therapy group including: eight (13%) of 64 patients reporting rash, and colitis, gastritis, pancreatitis and arthritis, and diabetic ketoacidosis each occurring in one (2%) patient. There were two (3%) treatment related deaths, one in the nivolumab group and one in the triplet therapy group. The overall response rate was 76% (95% CI 53-92) in the ipilimumab group, 89% (65-99) in the nivolumab group, and 82% (60-95) in the triplet therapy group, and the complete response rate was 57% (95% CI 34-78%) in the ipilimumab group, 61% (36-83%) in the nivolumab group, and 73% (50-89%) in the triplet therapy group. With a median follow-up of 2·6 years (IQR 1·8-2·9) in the ipilimumab group, 2·4 years (2·2-2·6) in the nivolumab group, and 1·7 years (1·6-1·9) in the triplet therapy group, median progression-free survival is 1·2 years (95% CI 1·7-not reached) in the ipilimumab group, but was not reached in the other two treatment groups. Median overall survival has not been reached in any of the groups. INTERPRETATION: There are clear differences in activity and toxicity of the three combination regimens. The tolerability and preliminary activity for the two most active regimens, brentuximab vedotin with nivolumab and the triplet therapy, are being compared in a randomised phase 2 trial (NCT01896999). FUNDING: Eastern Cooperative Oncology Group-American College of Radiology Imaging Network and the National Cancer Institute of the National Institutes of Health.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Ipilimumab/uso terapêutico , Nivolumabe/uso terapêutico , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Progressão da Doença , Quimioterapia Combinada , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Hipersensibilidade/etiologia , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Dor/etiologia , Intervalo Livre de Progressão , Recidiva , Taxa de Sobrevida , Resultado do Tratamento
8.
Pediatrics ; 146(Suppl 1): S18-S24, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32737228

RESUMO

With a few notable exceptions, adolescents do not possess the legal authority to provide consent for or refuse medical interventions. However, in some situations, the question arises regarding whether a mature minor should be permitted to make a life-altering medical decision that would be challenged if made by the minor's parent. In this article, I explore what we currently know about the adolescent brain and how that knowledge should frame our understanding of adolescent decision-making. The prevailing approach to determining when adolescents should have their decisions respected in the medical and legal context, an approach that is focused on establishing capacity under a traditional informed consent model, will be reviewed and critiqued. I will suggest that the traditional model is insufficient and explore the implications for the adolescent role in health care decision-making.


Assuntos
Desenvolvimento do Adolescente , Encéfalo/crescimento & desenvolvimento , Tomada de Decisão Clínica , Doença de Hodgkin/tratamento farmacológico , Consentimento Livre e Esclarecido/psicologia , Recusa do Paciente ao Tratamento/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Fatores Etários , Feminino , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Competência Mental/legislação & jurisprudência , Competência Mental/psicologia , Mães , Patient Self-Determination Act , Autonomia Pessoal , Recusa do Paciente ao Tratamento/legislação & jurisprudência , Estados Unidos
9.
Ann Hematol ; 99(10): 2385-2392, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32748163

RESUMO

Up to 30% of patients with classical Hodgkin lymphoma (cHL) are not responsive to frontline therapy or relapse after primary treatment. In these cases, autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care. The combination of brentuximab vedotin and bendamustine (BV + B) is an effective salvage regimen in this challenging subpopulation. This nationwide multicenter study investigated the real-world efficacy and safety of the BV + B regimen as a bridge to AHSCT in patients with primary refractory or relapsed cHL. A total of 41 cHL patients underwent AHSCT after receiving at least 1 cycle of BV + B (with brentuximab vedotin given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1-2 every 4 weeks). After a median of 3 (1-6) cycles of BV + B, the objective response rate was 78%, with 29 (70.7%) patients achieving complete remission. Twelve (29.3%) patients relapsed after AHSCT, 2 (4.9%) of them died, while 2 (4.9%) patients are lost to follow-up. After a median of 17 months of follow-up, the estimated 2-year overall- and progression-free survival after AHSCT was 93 and 62%, respectively. Features of advanced disease at recurrence (p = 0.038) and the presence of stage IV cHL at relapse (p = 0.024) are strong predictor markers of unfavorable outcomes. Twenty-four (58.5%) patients experienced adverse events of any grade, while no grade IV toxicities were reported. BV + B is an effective salvage option with a manageable toxicity profile in cHL. The real-world safety and efficacy of this combination are similar to the observations made on the study population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Brentuximab Vedotin/administração & dosagem , Brentuximab Vedotin/efeitos adversos , Terapia Combinada , Avaliação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Neutropenia/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
11.
Cancer Treat Rev ; 88: 102042, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32521386

RESUMO

Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells.


Assuntos
Doença de Hodgkin/imunologia , Doença de Hodgkin/terapia , Imunoterapia/métodos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/terapia , Imunidade Adaptativa , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Imunidade Inata , Ensaios Clínicos Controlados Aleatórios como Assunto , Linfócitos T/imunologia
12.
J Comput Assist Tomogr ; 44(4): 619-626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32558769

RESUMO

OBJECTIVE: The aim of the study was to study clinical, imaging findings, response patterns, and immune-related adverse events in classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) patients treated with immune checkpoint inhibitors (ICIs). METHODS: A retrospective search was performed to identify patients with relapsed/refractory cHL and NHL treated with ICIs from 2015 to 2019. Clinical and laboratory data were collected. Imaging studies were reviewed for treatment response and immune-related adverse events. RESULTS: Ten patients with relapsed/refractory cHL (median age, 41 years) and 14 patients with relapsed/refractory NHL (median age, 61 years) were identified. Overall response rate was 70% for cHL patients. None of the NHL patients demonstrated complete or partial response. One case of hyperprogression and one case with atypical response were radiologically detected in cHL patients. Hypothyroidism requiring treatment occurred in 2 (20%) of 10 cHL patients, one of which had imaging correlate. Of 14 NHL patients, 1 (7%) had radiologic evidence of pneumonitis and 1 (7%) had colitis. CONCLUSIONS: This single-institution observational study demonstrated that overall response rate was higher in patients with cHL undergoing ICI. Immune checkpoint inhibitor therapy has unique response patterns and toxicities in both cHL and NHL patients that radiologists should keep in mind.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Colite/epidemiologia , Doença de Hodgkin/tratamento farmacológico , Hipotireoidismo/epidemiologia , Linfoma não Hodgkin/tratamento farmacológico , Pneumonia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Colite/induzido quimicamente , Feminino , Doença de Hodgkin/diagnóstico por imagem , Humanos , Hipotireoidismo/induzido quimicamente , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Pneumonia/induzido quimicamente , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
13.
Pediatr Blood Cancer ; 67(8): e28365, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32491274

RESUMO

Hepatic involvement in Hodgkin lymphoma (HL) is uncommon (∼5% of patients) but always implies stage IV disease. Accurate staging is mandatory for making the appropriate risk assignment and treatment decisions. The Staging Evaluation and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) international working group conducted a systematic literature review of liver involvement in HL patients with the aim to propose a universally acceptable definition for liver involvement in pediatric HL. Thirty-three articles describing 6985 pediatric and adult HL patients were reviewed, of which 539 (7.7%) mentioned liver involvement. The literature did not provide a uniform definition of hepatic involvement and we propose consensus criteria derived from the EuroNet and Children's Oncology Group protocols, where liver involvement is defined as any hepatic lesion on computed tomography scan that correlates with 18 F-FDG uptake greater than background liver. A clear definition of liver lesions is necessary to consistently identify liver involvement and compare its impact on outcomes among protocols worldwide.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Lactente , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Estadiamento de Neoplasias , Adulto Jovem
14.
Clin Nucl Med ; 45(8): 652-653, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32520507

RESUMO

We present an asymptomatic 70-year-old man referred for an F-FDG PET/CT for initial staging of a Hodgkin lymphoma. F-FDG PET/CT showed bilateral cervical lymphadenopathy (stage II). Incidentally, the CT demonstrated bilateral ground-glass opacities with low-grade F-FDG activity. CT findings were suspicious for COVID-19 pneumonitis. The COVID-19 reverse transcriptase polymerase chain reaction (RT-PCR) examination result was negative. Given the high clinical suspicion for COVID-19, the patient was isolated and repeat RT-PCR was positive at 72 hours. RT-PCR may be falsely negative in early COVID-19 disease, even with positive CT findings.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Doença de Hodgkin/complicações , Pneumonia Viral/diagnóstico por imagem , Idoso , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Fluordesoxiglucose F18 , Humanos , Masculino , Pandemias , Pneumonia Viral/complicações , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
15.
Clin Nucl Med ; 45(8): 644-646, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32520506

RESUMO

We report the results of F-FDG PET/CT in an asymptomatic case of COVID-19 infection. A 27-year-old woman underwent FDG PET/CT for revaluation of a stage IIIE B Hodgkin lymphoma after the fourth cycle of chemotherapy. It showed intense avid FDG subpleural mixed ground-glass and consolidative lesions, especially in the left lung. Because of this morpho-metabolic aspect and the epidemic context, a viral pneumopathy was suspected. The patient who was initially asymptomatic was admitted for fever 28 hours after the PET/CT. The nasopharyngeal swab was positive for COVID-19, and the outcome was favorable.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Doença de Hodgkin/complicações , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Betacoronavirus , Infecções por Coronavirus/complicações , Feminino , Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Humanos , Estadiamento de Neoplasias , Pandemias , Pneumonia Viral/complicações
16.
PLoS Pathog ; 16(6): e1008590, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32542010

RESUMO

EBV transforms B cells in vitro and causes human B-cell lymphomas including classical Hodgkin lymphoma (CHL), Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). The EBV latency protein, EBNA2, transcriptionally activates the promoters of all latent viral protein-coding genes expressed in type III EBV latency and is essential for EBV's ability to transform B cells in vitro. However, EBNA2 is not expressed in EBV-infected CHLs and BLs in humans. EBV-positive CHLs have type II latency and are largely driven by the EBV LMP1/LMP2A proteins, while EBV-positive BLs, which usually have type I latency are largely driven by c-Myc translocations, and only express the EBNA1 protein and viral non-coding RNAs. Approximately 15% of human BLs contain naturally occurring EBNA2-deleted viruses that support a form of viral latency known as Wp-restricted (expressing the EBNA-LP, EBNA3A/3B/3C, EBNA1 and BHRF1 proteins), but whether Wp-restricted latency and/or EBNA2-deleted EBV can induce lymphomas in humanized mice, or in the absence of c-Myc translocations, is unknown. Here we show that a naturally occurring EBNA2-deleted EBV strain (P3HR1) isolated from a human BL induces EBV-positive B-cell lymphomas in a subset of infected cord blood-humanized (CBH) mice. Furthermore, we find that P3HR1-infected lymphoma cells support two different viral latency types and phenotypes that are mutually exclusive: 1) Large (often multinucleated), CD30-positive, CD45-negative cells reminiscent of the Reed-Sternberg (RS) cells in CHL that express high levels of LMP1 but not EBNA-LP (consistent with type II viral latency); and 2) smaller monomorphic CD30-negative DLBCL-like cells that express EBNA-LP and EBNA3A but not LMP1 (consistent with Wp-restricted latency). These results reveal that EBNA2 is not absolutely required for EBV to form tumors in CBH mice and suggest that P3HR1 virus can be used to model EBV positive lymphomas with both Wp-restricted and type II latency in vivo.


Assuntos
Infecções por Vírus Epstein-Barr , Antígenos Nucleares do Vírus Epstein-Barr/genética , Deleção de Genes , Herpesvirus Humano 4/fisiologia , Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Proteínas Virais/genética , Latência Viral , Animais , Linhagem Celular , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/patogenicidade , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Camundongos , Proteínas Virais/metabolismo
17.
Ann Hematol ; 99(11): 2565-2576, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32507911

RESUMO

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Nivolumabe/administração & dosagem , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Transplante de Células-Tronco , Taxa de Sobrevida
18.
Ann Hematol ; 99(7): 1575-1581, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32500223

RESUMO

This study investigated the clinical characteristics of Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (HLH-HL). Clinical data of 8 patients with HLH-HL and 20 non-HLH-HL patients were included. All eight HLH-HL patients tested positive for plasma Epstein-Barr virus (EBV)-DNA and EBV-encoded small RNA (EBER), and six patients were positive for EBV-DNA in the peripheral blood mononuclear cells (PBMCs). Two out of the 20 non-HLH-HL patients were confirmed positive for EBER, and the remaining 18 patients were negative. Among the HLH-HL patients, five patients received ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) chemotherapy regimens in other hospitals, and their conditions were considered to be worse, for which reason they were transferred to our center, and three patients were treated with DEP (doxorubicin-etoposide-methylprednisolone) regimens to target HLH and were alive as of the writing of this article. Two patients were critically ill upon admission and were not able to undergo chemotherapy. Significant differences in survival time were observed between the HLH-HL and non-HLH-HL patients (P = 0.005). HL patients found positive for EBV (plasma/PBMCs EBV-DNA(+)/EBER(+)) may be more likely to develop HLH-HL. It may be beneficial to target HLH during the acute phase of HLH, followed by treating HL once the HLH condition has stabilized. HLH-HL patients have worse prognosis and higher mortality than non-HLH-HL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Estudos de Casos e Controles , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Etoposídeo/uso terapêutico , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/sangue , Doença de Hodgkin/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
19.
Medicine (Baltimore) ; 99(21): e20048, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481271

RESUMO

RATIONALE: Ustekinumab is a biological agent that inhibits interleukin 12 and 23 and has been approved for the treatment of moderate and severe plaque psoriasis. There have been case reports that raise concerns about its oncogenic potential. We are the first authors to report a case of Hodgkin lymphoma in a psoriatic patient receiving ustekinumab. PATIENT CONCERNS: A 22-year-old asymptomatic female patient presented to our department to investigate an enlarged cervical lymph node. Her past history was unremarkable, except for psoriasis since age 13. Two months before presentation the decision to administer Ustekinumab was taken and the patient had already received 3 doses. DIAGNOSES: During workup a Stage IV Hodgkin lymphoma was discovered. INTERVENTIONS: Ustekinumab administration was discontinued. The patient received treatment with the ABVD regimen. OUTCOMES: The patient's disease was refractory to the above-mentioned treatment. Therefore, a more aggressive regimen (BEACOPP escalated) was administered. LESSONS: Growing postmarketing surveillance data and case reports indicate that further research is warranted in order to elucidate a potential association between Ustekinumab and malignancy.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Doença de Hodgkin/induzido quimicamente , Psoríase/tratamento farmacológico , Ustekinumab/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Ustekinumab/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
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