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Linfomas primários do sistema nervoso central – fisiopatologia, diagnóstico e terapêutica
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Orientador(es)
Resumo(s)
O linfoma primário do sistema nervoso central é um linfoma não-Hodgkin agressivo e extranodal difuso de grandes células B. Estes linfomas têm origem no cérebro, espinal-medula, olhos ou leptomeninges, na ausência de doença sistémica prévia ou concomitante. Representam aproximadamente 4% das neoplasias intracranianas e 2% a 3% dos linfomas não-Hodgkin, com uma taxa de incidência anual de 0,47 casos por 100.000 pessoas-ano.
A quimioterapia baseada em doses elevadas de metotrexato tem um papel fundamental no tratamento dos linfomas primários do sistema nervoso central. Contudo, a eficácia dos fármacos é limitada por vários factores, entre os quais se incluem as características funcionais e microambientais do sistema nervoso central. A acção protectora da barreira hemato-encefálica é também um factor limitante para a acção dos agentes quimioterapêuticos mais eficazes.
A associação de quimioterapia com a radioterapia de irradiação cerebral total melhora as taxas de resposta e de sobrevida, quando comparada com a quimioterapia isolada, mas há um aumento do risco de neurotoxicidade com o recurso a radioterapia de irradiação total.
Os agentes quimioterapêuticos actualmente utilizados no tratamento destes doentes poderão em breve atingir todo o seu potencial no que diz respeito ao aumento das taxas de sobrevida destes doentes. É, deste modo, necessário o desenvolvimento de novas terapias, que possam proporcionar uma melhoria na taxa de sobrevida e, ao mesmo tempo, assegurar a qualidade de vida dos doentes.
A pesquisa de novos biomarcadores que permitam a identificação de grupos de doentes de alto risco é também uma necessidade a ser colmatada no futuro.
Primary central nervous system lymphoma is an aggressive extranodal non-Hodgkin lymphoma of the diffuse large B cell type. These lymphomas arise from the brain, spinal cord, eyes or leptomeninges, in the absence of prior or concurrent systemic disease. PCNSL accounts for approximately 4% of intracranial neoplasms and 2% to 3% 6% of non-Hodgkin lymphomas with a yearly incidence rate of 0.47 cases per 100,000 person-years. Chemotherapy has a fundamental role in the management of PCNSL. However, the efficacy of the drugs in use is limited by several factors including the functional and microenvironment characteristics of the central nervous system. The protection provided by the blood-brain barrier is also a limiting factor for the action of the most effective chemotherapeutic agents. High dose methotrexate based chemotherapy is the standard therapy in the treatment of primary central nervous system lymphomas. The association of chemotherapy with whole brain radiation therapy improves response rates and survival when compared to chemotherapy alone, but there is an increased risk for neurotoxicity with whole brain radiation therapy. The chemotherapeutic agents currently used to treat these patients may soon reach its full potential with regard to increasing survival rates. Thus, there is a need for developing novel therapies that can provide an improvement in survival rates and at the same time ensure the patients quality of life. The search for new biomarkers that allow the identification of subpopulations of patients at high risk is also a need to be addressed in future.
Primary central nervous system lymphoma is an aggressive extranodal non-Hodgkin lymphoma of the diffuse large B cell type. These lymphomas arise from the brain, spinal cord, eyes or leptomeninges, in the absence of prior or concurrent systemic disease. PCNSL accounts for approximately 4% of intracranial neoplasms and 2% to 3% 6% of non-Hodgkin lymphomas with a yearly incidence rate of 0.47 cases per 100,000 person-years. Chemotherapy has a fundamental role in the management of PCNSL. However, the efficacy of the drugs in use is limited by several factors including the functional and microenvironment characteristics of the central nervous system. The protection provided by the blood-brain barrier is also a limiting factor for the action of the most effective chemotherapeutic agents. High dose methotrexate based chemotherapy is the standard therapy in the treatment of primary central nervous system lymphomas. The association of chemotherapy with whole brain radiation therapy improves response rates and survival when compared to chemotherapy alone, but there is an increased risk for neurotoxicity with whole brain radiation therapy. The chemotherapeutic agents currently used to treat these patients may soon reach its full potential with regard to increasing survival rates. Thus, there is a need for developing novel therapies that can provide an improvement in survival rates and at the same time ensure the patients quality of life. The search for new biomarkers that allow the identification of subpopulations of patients at high risk is also a need to be addressed in future.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014
Palavras-chave
Linfoma Primário do Sistema Nervoso Central Quimioterapia Irradiação cerebral total Metotrexato Rituximab Transplante de células estaminais hematopoiéticas Neurotoxicidade Disrupção da barreira hemato encefálica Mestrado Integrado - 2014