RESUMO
PURPOSE OF REVIEW: The review highlights the recent advances in the pathogenesis, diagnosis and treatment of AIDS-related primary CNS lymphoma (AIDS-PCNSL). RECENT FINDINGS: The incidence of AIDS-PCNSL has decreased in the era of highly active antiretroviral therapy (HAART). The prognosis has improved and this most probably in relation both with the HAART-induced immunologic status recovery and subsequently the possibility to use more aggressive treatment strategies. Immunomodulatory effect of HAART seems also to have an indirect antitumor activity on the disease. SUMMARY: The treatment strategy for AIDS-PCNSL in the HAART era tends to become similar to that of the immunocompetent population. In the absence of randomized trials devoted to AIDS-PCNSL, most current national comprehensive cancer network guidelines recommend the use of high-dose methotrexate-based chemotherapy combined or not with whole-brain radiotherapy as initial treatment in addition to HAART. The objective for the future would be that prognosis of AIDS-PCNSL catch up with that of the immunocompetent patients with special attention to systemic and neurocognitive tolerance of the treatments.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , Linfoma Relacionado a AIDS/terapia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/imunologia , Terapia Antirretroviral de Alta Atividade , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/imunologia , Neoplasias do Sistema Nervoso Central/virologia , Humanos , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/virologiaRESUMO
A20, a negative regulator of NF-κB, has been implicated as a tumor suppressor gene in multiple types of B-cell lymphoma. AIDS-related lymphomas (ARLs) are high-grade B-cell lymphomas that are frequently associated with EBV infection. We examined a panel of ARLs for A20 alterations. FISH showed A20 deletion in 6 of 33 cases (18%). A20 mutations were found in 3 of 19 cases (16%), including 2 cases with deletions of the comple-mentary allele. Immunohistochemistry showed the absence of A20 protein in 7 of 55 samples (13%). In contrast to reports in Hodgkin lymphoma in which EBV infection and A20 alteration are mutually exclusive, A20 inactivation was observed in both EBV(+) and EBV(-) cases. The EBV latent membrane protein 1, which activates NF-κB, was not expressed in 12 of 13 cases with A20 loss. In ARLs loss of A20 may be an alternative mechanism of NF-κB activation in the absence of latent membrane protein 1 expression.
Assuntos
Infecções por Vírus Epstein-Barr/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Linfoma Relacionado a AIDS/genética , Linfoma Relacionado a AIDS/virologia , Mutação , Proteínas Nucleares/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA , Infecções por Vírus Epstein-Barr/metabolismo , Deleção de Genes , Inativação Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfoma Relacionado a AIDS/metabolismo , NF-kappa B/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Proteínas da Matriz Viral/metabolismoRESUMO
The relationship between clinical and molecular characteristics of 45 treated individuals with histologically-documented human immunodeficiency virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to determine whether differences in molecular features of lymphoma were associated with differences in clinical outcome. Tissue specimens from these tumors were evaluated for evidence of Ig heavy-chain gene rearrangements using both Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Lymphomas were also evaluated for the presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gene rearrangements. Twenty-five lymphomas were characterized as polyclonal and 20 as monoclonal. PCR amplification of expressed Ig variable (V)-region genes confirmed polyclonality in three extensively studied polyclonal lymphomas. The median CD4 count was significantly higher in the group with polyclonal disease (277/microL) than in the group with monoclonal disease (123/microL), P = .04. The complete response rate to therapy was significantly higher in patients with polyclonal disease (78%) and CD4 greater than 200/microL (81%) than in those with monoclonal disease (31%) and CD4 less than 200/microL (33%). CD4 count, clonality, and presence of EBV DNA sequences were the most important predictors of survival. Both Kaplan-Meier and Cox proportional hazards analyses showed a markedly prolonged survival in those patients with both CD4 > or = 200/microL and polyclonal disease. Histologically the polyclonal lymphomas were high grade in appearance and contained prominent macrophages. All seven surviving patients were in this group. Median survival for those individuals whose tumors contained EBV sequences was only 3.2 months (range, 0.4 to 19.5), whereas those with EBV- tumors survived for a median of 9.0 months (range, 0.7 to 65.2), P = .0007. These data indicate that molecular features of HIV-associated lymphomas may be important predictors of clinical outcome. These characteristics define a distinct subset of patients with polyclonal EBV- tumors and CD4 counts greater than 200/microL that appear to have a less aggressive clinical course.