RESUMEN
Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.
A cincuenta años de los primeros reportes de asociación del linfoma de Burkitt con el virus de Epstein-Barr (VEB), el VEB ha emergido como el tercer virus de tipo oncogénico con mayor prevalencia a escala mundial. La infección por VEB se asocia con diversas neoplasias, incluyendo el linfoma de Hodgkin y el no Hodgkin, linfoma de células T/NK y carcinoma nasofaríngeo. A pesar del control inmunológico altamente específico en el huésped inmunocompetente, el VEB puede ocasionar complicaciones severas en el huésped inmunocomprometido (es decir, la enfermedad linfoproliferativa post-trasplante). Esto es un problema particularmente en pacientes en quienes se retrasa la reconstitución de la inmunidad después de un trasplante de células madre hematopoyéticas o un trasplante de órganos sólidos. A pesar de los avances en las técnicas de diagnóstico y los algoritmos de tratamiento que permiten la identificación temprana y el tratamiento de pacientes de alto riesgo, las tasas mortalidad siguen siendo muy altas (del 90%) si no se recibe tratamiento temprano. La piedra angular del tratamiento incluye la disminución de la inmunosupresión y la depleción de células B in vivo con un anticuerpo monoclonal anti-CD20. Sin embargo, estas modalidades de tratamiento no son siempre posibles debido al rechazo del injerto, la enfermedad de injerto contra huésped y la toxicidad. Nuevas modalidades de tratamiento incluyen el uso de la terapia adoptiva de células T, que ha mostrado resultados promisorios en diversas neoplasias relacionadas con el VEB. En este artículo se revisan los avances más recientes en cuanto a los factores de riesgo, diagnóstico y tratamiento de las neoplasias asociadas con VEB, particularmente la enfermedad linfoproliferativa post-trasplante. También se discuten los tratamientos más recientes e innovadores, que incluyen la terapia adoptiva de células T así como el manejo de situaciones especiales, como la infección crónica activa de VEB y la linfohistiocitosis hemafagocítica asociada con VEB.
RESUMEN
Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.