Browsing by Author "Marques, H"
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- Análise económica do rituximab, em associação com ciclofosfamida, vincristina e prednisolona no tratamento de doentes com linfoma folicular avançado em PortugalPublication . Braga, P; Carvalho, S; Gomes, M; Guerra, L; Lúcio, P; Marques, H; Negreiro, F; Pereira, C; Silva, C; Teixeira, AOBJECTIVE: Evaluate costs and benefits of rituximab in combination with cyclophosphamide/vincristine/prednisolone chemotherapy regimen (R-CVP), in previously untreated patients with indolent non-Hodgkin lymphoma (NHL), compared to CVP alone from a Portuguese National Health System (NHS) perspective. METHODS: Cost-effectiveness (Life Years Gained--LYG) and cost-utility analysis (Quality Adjusted Life Years--QALYs) were performed for a time horizon of 10 years, according to a Markov economic model with three health states (progression free survival, progression and death) and monthly cycles for a population of previously untreated patients with indolent NHL. Data from a phase III clinical trial was used and expanded to include unpublished 53-month median follow-up data. Survival after first-line therapy was estimated from the Scotland and Newcastle Lymphoma Group registry data and utilities were derived from a study in the UK performed in patients with follicular lymphoma. Resource consumption was estimated by a Portuguese expert panel (Delbecq Panel). Costs were calculated from the Portuguese NHS perspective through official data with prices updated to 2008. Only direct medical costs were considered. Costs and clinical outcomes were discounted at 5% per annum. Deterministic and probabilistic sensitivity analysis were performed around assumptions on the time horizon, costs, utilities and excess mortality rate due to progression applied in the base-case analysis. RESULTS: The 10-year base-case analysis showed a lower total cost per patient with CVP alone (€ 85,838) in comparison with R-CVP (€ 87,774). Life expectancy and Quality adjusted life expectancy per patient were higher with R-CVP (6.361 and 4.166, respectively) than with CVP alone (5.557 and 3.438, respectively), representing increases of 0.804 in LYG and 0.728 (8.7 months) in QALYs gained. The incremental cost per LYG was € 2,407 and the incremental cost per QALY gained was € 2,661. The probabilistic sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS: This study demonstrates that the combination R-CVP in previously untreated indolent NHL patients improves life expectancy and is a cost-effective alternative to CVP in Portugal.
- Association of adult mastocytosis with M541L in the transmembrane domain of KITPublication . Rocha, J; Duarte, ML; Marques, H; Torres, F; Tavares, P; Silva, A; Brito, C
- Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosisPublication . Marques, H; Catarino, R; Domingues, N; Barros, E; Portela, C; Almeida, MI; Costa, S; Reis, RM; Medeiros, R; Longatto-Filho, AThe Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or β-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.
- Hérnia de Spiegel: descrição de caso clínico com análise da literaturaPublication . Goulart, A; Marques, H; Reis, M
- Hotspot TERT promoter mutations are rare events in testicular germ cell tumorsPublication . Cárcano, FM; Vidal, DO; van Helvoort Lengert, A; Neto, CS; Queiroz, L; Marques, H; Baltazar, F; da Silva Martinelli, CM; Soares, P; da Silva, EC; Lopes, LF; Reis, RMThe abnormal activation of telomerase, codified by the telomerase reverse transcriptase (TERT) gene, is related to one of cancer hallmarks. Hotspot somatic mutations in the promoter region of TERT, specifically the c.-124:C>T and c.-146:C>T, were recently identified in a range of human cancers and have been associated with a more aggressive behavior. Testicular germ cell tumors frequently exhibit a good prognosis; however, the development of refractory disease is still a clinical challenge. In this study, we aim to evaluate for the first time the presence of the hotspot telomerase reverse transcriptase gene promoter mutations in testicular germ cell tumors. A series of 150 testicular germ cell tumor cases and four germ cell tumor cell lines were evaluated by PCR followed by direct Sanger sequencing and correlated with patient's clinical pathological features. Additionally, we genotyped the telomerase reverse transcriptase gene promoter single nucleotide polymorphism rs2853669 (T>C) located at -245 position. We observed the presence of the TERT promoter mutation in four patients, one exhibited the c.-124:C>T and three the c.-146:C>T. No association between TERT mutation status and clinicopathological features could be identified. The analysis of the rs2853669 showed that variant C was present in 22.8 % of the cases. In conclusion, we showed for the first time that TERT promoter mutations occur in a small subset (~3 %) of testicular germ cell tumors.
- Indeterminate cell histiocytosis in association with acute myeloid leukemiaPublication . Ventura, F; Pereira, T; Duarte, ML; Marques, H; Pardal, F; Brito, CIndeterminate cell histiocytosis (ICH) is a rare proliferative disorder, in which the predominant cells share morphologic and immunophenotypic features from both Langerhans and non-Langerhans cell histiocytosis. We describe a 62-year-old man presenting a 2-month history of firm nodular lesions on the upper lip. Histopathology, immunohistochemical, and ultrastructural analysis showed typical findings of ICH. The patient was treated with thalidomide and almost complete regression of the lesions was reached within 7 months. Nevertheless, one month after remission, he developed an acute myeloid leukemia of the subtype monocytic leukemia (M5). The patient's condition rapidly worsened and he died due to a respiratory failure four weeks later. We present this case because apart of being rare it joins the effectiveness of thalidomide and the association with an acute monocytic leukemia. A review of the literature is made.
- Intracardiac mass from Burkitt's lymphoma in an immunocompromised patient: a very rare form of presentationPublication . Vilaça, A; Monteiro, M; Pimentel, T; Marques, H
- Linfomas não-Hodgkin extraganglionares: uma análise retrospectivaPublication . Trindade, I; Almeida, M; Coimbra, F; Portela, C; Esperança, S; Marques, HNa maioria dos linfomas não-Hodgkin (LNH), o envolvimento extra-ganglionar surge durante o curso da doença. Contudo alguns LNH têm origem em locais que não os gânglios linfáticos ou o baço, sendo designados por LNH extra-ganglionares. Este estudo tem como objectivo ilustrar as características clínico-patológicas dos doentes com LNH extra-ganglionares primários (LNH-EP). Foram avaliados 125 casos de LNH, dos quais 37 (30%) foram considerados LNH-EP. A proporção entre os sexos foi de 1:1, com uma média de idades de 61 anos. Surgiram 8 casos (20%) de LNH de fenótipo T e 29 casos (80%) de LNH de fenótipo B. Os locais mais atingidos foram a pele em 12 casos (32,4%) e o trato gastrointestinal em 11 (29,7%); 24% tinham sintomas B; 81% eram localizados (estadio IE e IIE). De acordo com a histologia, segundo a classificação da OMS, 1 caso (3%) era altamente agressivo (linfoma de Burkitt), 68% agressivos e 29% indolentes. O linfoma B difuso de grandes células (LNH B DGC) constitui 51% e o linfoma de MALT 14% de todos os casos. O índice de prognóstico internacional (IPI) demonstrou que 7% dos doentes pertenciam ao grupo de risco alto, 3% intermédio alto, 20% risco intermédio baixo e 70% risco baixo. Em conclusão, os LNH-EP são um grupo heterogéneo de doenças, sendo as localizações mais frequentes a pele e o trato gastrointestinal. Há uma maior percentagem de LNH T extra-ganglionar do que o descrito para o LNH ganglionar. O tipo histológico mais frequente foi o LNH B DGC. O IPI revelou-se discriminativo relativamente à sobrevivência, mas a sua aplicabilidade nos LNH extra-ganglionares é questionável, porque não divide homogeneamente os doentes. (Discussão) (...) A classificação hematológica das neoplasias para a OMS divide as neoplasias em células B, células T e células 'natural killer'. A importância desta classificação histológica reside no comportamento clínico (indolente, agressivo, muito agressivo) do LNH em questão. Os LNH indolentes (centro-folicular, zona marginal incluíndo MALT, micose fungóide) têm sobrevivência longa mesmo sem tratamento; os LNH agressivos e muito agressivos têm cura mas são rapidamente fatais se não forem tratados ou se se revelarem resistentes. No nosso estudo não foi possível estabelecer uma relação entre sobrevivência aos 12 meses nos LNH indolentes comos agressivos. No grupo dos LNH muito agressivos (l. Burkitt) só existiu 1 caso, que permaneceu vivo e sem doença até ao fim do estudo. Os que tinham doença localizada tiveram sobrevivência maior do que os que tinham doença disseminada, não sendo possível contudo estabelecer uma correlação estatisticamente significativa. Este achado parece-nos relevante, e pode não ser inteiramente inesperado: o sistema de estadiamento de Ann Arbor foi criado para a estratificação de doentes com linfoma de Hodgkin, que ao contrário dos LNH evolui e progride por patamares sequenciais, atingindo as cadeias ganglionares a partir de um gânglio patológico. Quanto à biologia do LNH, o processo é diferente, podendo haver doença extra-ganglionar ou atingimento da medula óssea apesar de escassa massa tumoral ganglionar, o que traduz uma insuficiente correlação entre a massa tumoral e o patamar de evolução, mensurado pelo sistema de Ann Arbor no caso de LNH. A incapacidade discriminativa deste sistema para medir a massa tumoral e o prognóstico levou ao aparecimento do IPI (índice prognóstico internacional), especificamente adaptado ao LNH de alto grau. Posteriormente surgiram o FLIPI e MIPI adaptados do linfoma folicular e de células do manto, respectivamente. Neste trabalho confirmou-se que o sistema de Ann Arbor não é útil para os LNH extra-ganglionares. Demonstrou-se que existe uma correlação estatisticamente significativa nos doentes com DHL elevada e IPI de alto grau, associando-se uma maior mortalidade. A utilidade clínica do IPI no LNH extra-ganglionar levanta no entanto alguma dificuldade, já que estratifica mal os doentes; a maioria pertencia ao grupo de baixo risco e só 10% estavam no grupo de alto risco, onde se pode prever uma evolução mais agressiva. Uma vez que o nosso estudo é retrospectivo e tem uma amostra reduzida, as conclusões devem ser tomadas com precaução. Será necessário um aumento da amostra em estudo e/ou a conjugação com dados de outros centros para se estabelecerem premissas com maior poder estatístico. (Conclusão) Os linfomas cutâneos e do trato gastrointestinal demonstraram ser os mais prevalentes, assim como o subtipo histológico de LNH difuso de grandes células. O IPI demonstrou ser um factor discriminatório na sobrevida dos doentes, mas não estratifica os doentes por grupos homogéneos, e portanto é de utilização duvidosa nos LNH extra-ganglionares.
- Palliative splenic irradiation for symptomatic splenomegaly in non-Hodgkin lymphomaPublication . Oliveira, LC; Fardilha, C; Louro, M; Pinheiro, C; Sousa, A; Marques, H; Costa, PINTRODUCTION AND AIMS: Splenic marginal zone lymphoma, an uncommon subtype of non-Hodgkin lymphoma (NHL), is usually present with symptomatic splenomegaly. Although splenectomy has long been considered the first-line therapy in symptomatic or cytopenic patients, it can lead to significant morbidity and mortality. Splenic irradiation is an option for patients who have a poor response to systemic therapy and/or are not surgical candidates. In this paper, we present a case report of a patient who received splenic radiotherapy for symptomatic splenomegaly. METHODS: An 85-year-old Caucasian man with a 4 year history of low-grade NHL presented with progressive pancytopenia, significant weight loss and symptomatic splenomegaly (abdominal discomfort, sense of fullness and limitation of mobility due to spleen size). The patient refused splenectomy and, in December 2017, was referred to palliative splenic radiotherapy. He was initially treated with five fractions of one Grey (Gy) in order to evaluate clinical and haematology response. After that, 1.5 Gy daily, 5 days a week for 3 weeks. 3D conformal radiotherapy, multiple fields and mixed energy (6 and 15 Mv) were used. RESULTS: Radiotherapy allowed significant splenic reduction to almost half the size, resolving abdominal discomfort and improving quality of life. There was no decline of haemoglobin, leukocytes and platelet counts; in fact, there was a marginal increase. CONCLUSION: Palliative splenic irradiation was well tolerated confirming that it is a safe treatment option for palliation of symptomatic splenomegaly. Thereby, splenic irradiation should be strongly considered in the management of symptomatic splenomegaly, for selected patients who are refractory to or unsuitable for other options or when the patient refuses other treatments.
- Recomendações para o diagnóstico, tratamento e monitorização da leucemia mielóide crónicaPublication . Almeida, A; Castro, I; Coutinho, J; Guerra, L; Marques, H; Pereira, AMChronic Myeloid Leukemia (CML) is a clonal stem cell disease characterized by the expression of the fusion protein bcr-abl1, which has deregulated tirosine-kinase activity. Tyrosine kinase inhibitors (TKIs), and in particular imatinib, introduced fundamental changes in the treatment of CML, becoming, in most cases, the first-line treatment of choice in the chronic phase of this disease. Compared to other available therapies imatinib results in a marked increase in overall survival, tolerability and quality of life. The introduction of second generation TKI, with increased potency against bcr-abl1, expanded the number of therapeutic options for this disease and offers an alternative for patients resistant or intolerant to imatinib or who have progressed to the accelerated phase under this therapy. In order to achieve optimal outcomes, TKI therapy must be managed rigorously, requiring a careful monitoring of treatment response in pre-established time periods, thus permitting disease evaluation and safe decision of the most adequate option. Despite the definition of the criteria for imatinib treatment response, the therapeutic strategies to adopt according to the responses obtained are less clear. The objective of this paper is to review the criteria for CML diagnosis, treatment and monitoring, with recommendations as to the most adequate therapeutic choice according to the response to TKI therapy. The paper also focuses the current lines of investigation and debate areas that in the short term can significantly change the therapeutic scenario in this disease. These recommendations, supported by published scientific evidence and by the clinical practice of the expert panel involved in their elaboration, may constitute an important instrument for a better understanding and standardisation of the treatment and monitoring of CML in Portugal.