Treatment of primary effusion lymphoma with highly active antiviral therapy in the setting of HIV infection
Ripamonti, Diegoa; Marini, Basilioa; Rambaldi, Alessandrob; Suter, Fredya
aInfectious Diseases Unit, Bergamo, Italy
bDivision of Hematology, Bergamo, Italy.
Correspondence to Diego Ripamonti, MD, Infectious Diseases Unit, Bergamo, Italy. E-mail: firstname.lastname@example.org
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 . It is invariably associated with HHV-8 and usually confined to the body cavities (pleural, pericardial and peritoneal), without detectable tumor masses . 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 . 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 . 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% .
Although PEL is a subtype of lymphoma traditionally requiring chemotherapy , alternative approaches have been reported with controversial outcomes.
Chen et al.  reported only one out of seven patients receiving HAART, along with chemotherapy, who was still alive after 270 days since diagnosis. A 16-month  and 31-month  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 . Luppi et al.  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 . 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 . 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)  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 .
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 . 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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