ABSTRACT The incidence of aggressive lymphoma in the setting of HIV infection is significantly increased relative to the general population. Combination antiretroviral therapy (cART) for HIV has reduced the incidence of these neoplasms and has significantly improved clinical outcome for those who do develop lymphoma and require chemotherapy. With the possible exception of those individuals with the most severe immunocompromise, patients with HIV-associated lymphoma can be treated with the same standard immuno-chemotherapy regimens used in the immunocompetent population with similar expectations for good clinical outcome. Infusional regimens like dose adjusted EPOCH-R appear to be highly effective first-line therapy and for relapsed patients high-dose chemotherapy with autologous stem cell support is well-tolerated and effective. However, it should be recognized that there are unique risks associated with management of lymphoma in this patient population. While opportunistic infections are no longer a significant cause of death, antiretroviral agents used for management of HIV infection may interact with chemotherapeutic agents and other adjunctive therapies making communication between the treating Oncologist and the patient's primary HIV treatment provider of prime importance.
SourceAvailable from: Maria Angeles Muñoz-Fernández[Show abstract] [Hide abstract]
ABSTRACT: Objective: Patients infected by the HIV type 1 (HIV-1) frequently show a general deregulation of immune system. A direct influence of HIV-1 particles on B-cell activation, proliferation and B-cell phenotype alterations has been recently described. Moreover, expression of activation-induced cytidinedeaminase (AID) mRNA, which is responsible for class switch recombination (CSR) and somatic hypermutation (SHM), was reported to be overexpressed in B cells exposed to HIV-1. Design: Study of primary human B cells in an in-vitro model. Methods: In the current study, we evaluated which signalling pathways are activated in primary B cells after a direct contact with HIV-1 particles in vitro using different kinase inhibitors. Results: Here, we report that B-cell activation together with the increase of AID mRNA expression and the subsequent class switch recombination (CSR) in HIV-exposed B cells occurred through spleen tyrosine kinase (SYK) and c-Jun N-terminal kinase (JNK) pathways. Conclusion: Therefore, we showed that HIV-1 could directly induce primary B-cell deregulation via SYK/B-cell receptor (BCR) engagement, and that activation was followed by the JNK pathway activation. To our knowledge, these data provide the first evidence that SYK/BCR activation was the first step for B-cell activation and CSR mechanism after HIV-1 stimulation in a T-cell-free context. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & WilkinsAIDS (London, England) 08/2014; 28(16). DOI:10.1097/QAD.0000000000000442 · 6.56 Impact Factor
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ABSTRACT: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive Non-Hodgkin lymphoma (NHL) over the last two decades. We performed a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials performed between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox-proportional hazard models to identify the association of patient-, lymphoma- and HIV-specific variables with the outcomes complete response, progression-free survival and overall survival in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004) and contemporary cART era (2005-2010). Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year overall survival was best in the contemporary era: 67% and 75% compared with 24 and 37% in the pre-cART era (P<0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50 /mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. Our results demonstrate a significant improvement of complete response rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative anti-lymphoma therapy for the majority of patients with aggressive NHL. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: firstname.lastname@example.org.Annals of Oncology 01/2015; 26(5). DOI:10.1093/annonc/mdv036 · 6.58 Impact Factor
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ABSTRACT: Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs.01/2015; 47(1):e136. DOI:10.1038/emm.2014.102