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Advisor(s)
Abstract(s)
O mieloma múltiplo é uma doença hemato-oncológica, em que ocorre proliferação de células plasmáticas malignas na medula óssea, tendo como consequência o surgimento de uma proteína monoclonal na corrente sanguínea e/ou na urina. A sua incidência é superior em indivíduos afro-americanos e do sexo masculino. A sua etiologia ainda permanece desconhecida, apesar de existirem alguns fatores associados ao seu aparecimento e desenvolvimento.
A presença de alterações genéticas pode ser importante na fisiopatologia do mieloma múltiplo e o microambiente da medula óssea é determinante na mediação da sobrevivência e da proliferação das células plasmáticas malignas, bem como na mediação da resistência à terapêutica e à angiogénese. As principais manifestações clínicas apresentadas pelos doentes são a anemia, a doença óssea, a insuficiência renal, o aumento do cálcio sanguíneo e uma maior predisposição para infeções.
O diagnóstico do mieloma múltiplo baseia-se numa avaliação clínica e laboratorial e requer a presença de, pelo menos, um evento definidor de mieloma, para além de plasmocitose medular clonal ≥10% ou plasmocitoma ósseo ou extra-medular, comprovado através de biópsia.
Tal como acontece noutras doenças oncológicas, no mieloma múltiplo a sobrevivência depende das características do doente, da carga e da biologia da doença, assim como da resposta à terapêutica. Esta sobrevivência tem vindo a aumentar ao longo dos últimos anos, não só pela disponibilidade de melhores técnicas de diagnóstico, como também pela incorporação do transplante autólogo de células estaminais hematopoiéticas e pela aprovação de novos agentes terapêuticos. Apesar disto, a doença ainda permanece incurável, pelo que muita investigação continua a existir nesta área, quer ao nível de novos biomarcadores, que sejam úteis no diagnóstico e no prognóstico, quer ao nível de novas abordagens terapêuticas. Neste sentido, a imunoterapia, mais especificamente a terapêutica com chimeric antigen receptor-T cells, mostra-se muito promissora, com resultados nunca antes observados com qualquer outra abordagem podendo, no futuro, vir a constituir uma alternativa em doentes para os quais todas as terapias atuais disponíveis já não são eficientes.
Multiple myeloma is a hematological disease, in which the proliferation of malignant plasma cells occurs in the bone marrow, resulting in the appearance of a monoclonal protein in the blood and/or urine. The incidence is higher in african american and male individuals. The etiology remains unknown, although there are some factors associated with its appearance and development. The presence of genetic changes can be important in the pathophysiology of multiple myeloma and the bone marrow microenvironment is decisive in mediating the survival and proliferation of malignant plasma cells, as well as in mediating resistance to therapy. The main clinical manifestations presented by patients are anaemia, bone disease, renal failure, hypercalcemia and an increased predisposition to infections. The diagnosis of multiple myeloma is based on a clinical and laboratory evaluation and requires the presence of, at least, one myeloma defining event, in addition to clonal bone marrow plasma cells ≥10% or biopsy proven bone or extramedullary plasmacytoma. As in other cancer diseases, survival in multiple myeloma depends on the patient's characteristics, disease burden and biology, as well as response to therapy. This survival has been increasing over the last few years, not only due to the availability of better diagnostic techniques, but also due to the incorporation of autologous hematopoietic stem cell transplantation and to the approval of new therapeutic agents. Despite this, multiple myeloma still remains an incurable disease and research continues to exist in this area, in terms of new biomarkers, which are useful both in diagnosis and prognosis, and in terms of new therapeutic approaches. In this sense, immunotherapy, more specifically, therapy with chimeric antigen receptor-T cells, is very promising, with results never seen before with any other approach, and may, in the future, become an alternative in patients for whom all current therapies available are no longer effective.
Multiple myeloma is a hematological disease, in which the proliferation of malignant plasma cells occurs in the bone marrow, resulting in the appearance of a monoclonal protein in the blood and/or urine. The incidence is higher in african american and male individuals. The etiology remains unknown, although there are some factors associated with its appearance and development. The presence of genetic changes can be important in the pathophysiology of multiple myeloma and the bone marrow microenvironment is decisive in mediating the survival and proliferation of malignant plasma cells, as well as in mediating resistance to therapy. The main clinical manifestations presented by patients are anaemia, bone disease, renal failure, hypercalcemia and an increased predisposition to infections. The diagnosis of multiple myeloma is based on a clinical and laboratory evaluation and requires the presence of, at least, one myeloma defining event, in addition to clonal bone marrow plasma cells ≥10% or biopsy proven bone or extramedullary plasmacytoma. As in other cancer diseases, survival in multiple myeloma depends on the patient's characteristics, disease burden and biology, as well as response to therapy. This survival has been increasing over the last few years, not only due to the availability of better diagnostic techniques, but also due to the incorporation of autologous hematopoietic stem cell transplantation and to the approval of new therapeutic agents. Despite this, multiple myeloma still remains an incurable disease and research continues to exist in this area, in terms of new biomarkers, which are useful both in diagnosis and prognosis, and in terms of new therapeutic approaches. In this sense, immunotherapy, more specifically, therapy with chimeric antigen receptor-T cells, is very promising, with results never seen before with any other approach, and may, in the future, become an alternative in patients for whom all current therapies available are no longer effective.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Mieloma múltiplo Fisiopatologia Diagnóstico Abordagem terapêutica Mestrado integrado - 2020