We report on an HIV-1 infected patient who was diagnosed with primary effusion lymphoma (PEL) and who achieved a long-term remission after treatment with only highly active antiviral therapy (HAART). In September 2005, a 42-year-old white homosexual man was referred to our clinic because he tested positive for HIV. He had a persistent low-grade fever, dry cough, asthenia and occasional dyspnoea, while his chest X-ray showed a left pleural effusion, unresponsive to empiric antibiotic treatment. Thoracentesis showed 350 ml of clear fluid with 1070 cells/ml (lymphocytes), 5.9 g/dl of proteins, 66 mg/ml of glucose, 4.667 and 307 U/l of lactate dehydrogenase (normal plasma value <460 U/l) in pleural effusion and plasma, respectively. Cytological and immunophenotipical analysis of pleural fluid showed large pleiomorphic cells CD45+, CD138+, CD3− and CD19−, respectively. PCR for human herpes virus 8 (HHV-8) DNA tested positive for both cells and plasma. A bone marrow biopsy was found normal. A total body computed tomography (CT) showed only a left pleural and a minimal pericardial effusions with a mild epatomegaly and splenomegaly without focal lesions. His cells/μl was 99 cells/mmc (4%) and plasma HIV RNA was 83.791 copies/ml. The patient was started on didanosine, lamivudine and ritonavir-boosted atazanavir. The HIV RNA was below 50 copies within 4 months and persistently remained undetectable, while his CD4 count progressively increased up to 318 cells/mmc (11%) at month 27. CT scan of the chest after 6 months confirmed a complete normalization of pleural effusion. The bone marrow biopsy after 12 months was normal as well as the chest X-ray at 24 months. The patient was still healthy at month 28. PEL is a rare disease and mostly described in the context of HIV infection [1,2], accounting for 0.1–4% of all HIV-associated non-Hodgkin's lymphoma [3]. It is invariably associated with HHV-8 and usually confined to the body cavities (pleural, pericardial and peritoneal), without detectable tumor masses [4]. Cytologically, it is a large-cell lymphoma of B-cell origin, with morphologic features bridging immunoblastic and anaplastic tumor cells and generally displays a null lymphocyte phenotype [2]. Its prognosis remains poor, even after the advent of HAART [2,5,6]. A median survival time of 6 months has been described in 11 patients with PEL, despite treatment with cytostatic drugs, or antivirals or both [3]. An additional large multicenter series (28 patients) showed a median survival time of 6.2 months and a 1-year overall survival rate of 39.3% [7]. Although PEL is a subtype of lymphoma traditionally requiring chemotherapy [2], alternative approaches have been reported with controversial outcomes. Chen et al.[2] reported only one out of seven patients receiving HAART, along with chemotherapy, who was still alive after 270 days since diagnosis. A 16-month [2] and 31-month [8] clinical remissions were reported in two patients treated with two nucleoside inhibitors (zidovudine plus zalcitabine) and a triple regimen (zidovudine plus lamivudine plus efavirenz) respectively, both without cytostatic therapy. However, failures of such a conservative approach have also been reported [9]. Luppi et al.[10] suggest a possible role for drugs active against HHV-8. One patient successfully used intracavity cidofovir and another one used a combination treatment of cidofovir, interferon-alpha and HAART, without chemotherapy. This latter patient was still alive after 28 months since PEL diagnosis [11]. A long-term (68 months) successful secondary prophylaxis with cidofovir, followed by valganciclovir, after a short course of cytostatic therapy and despite a failing concomitant HAART has been described in one patient [12]. Therefore, in this latter patient, anti-herpes-virus drugs proved effective in controlling HHV-8 viremia and PEL-associated clinical events, in the absence of immune reconstitution (CD4: 8 cells/mmc). The effect of HAART on HIV-associated malignancies is well known. In fact, both remission of Kaposi sarcoma (another HHV-8 related neoplasia) [13] and a reduced incidence of lymphomas have been described following the introduction of HAART [14,15]. The rationale for a conservative treatment reasonably lies in the HAART-induced immune reconstitution, which would not be the case in the event of PEL occurring in HIV negative patients on immunosuppressants or with advanced age [2]. Although available data are insufficient to define the most appropriate treatment for PEL in HIV context, our case confirms the possibility of a relatively long survival (28 months) after treatment with HAART, without cytostatic therapy. Only another case with a long survival (31 months) is reported in the literature [8]. These data suggest that, in the context of HIV, if PEL is limited and there is potential for HAART-induced immune recovery, avoiding chemotherapy might be an option.
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Sep 11, 2008
M.S Spitzer + 6
Open Access