Skip Navigation LinksHome > June 19, 2008 - Volume 22 - Issue 10 > Treatment of primary effusion lymphoma with highly active an...
AIDS:
doi: 10.1097/QAD.0b013e3282fc732b
Correspondence

Treatment of primary effusion lymphoma with highly active antiviral therapy in the setting of HIV infection

Ripamonti, Diegoa; Marini, Basilioa; Rambaldi, Alessandrob; Suter, Fredya

Free Access
Article Outline
Collapse Box

Author Information

aInfectious Diseases Unit, Bergamo, Italy

bDivision of Hematology, Bergamo, Italy.

Correspondence to Diego Ripamonti, MD, Infectious Diseases Unit, Bergamo, Italy. E-mail: diego.ripamonti@hotmail.com

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.

Back to Top | Article Outline

References

1. Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 1996; 88:645–656.

2. Chen YB, Rahemtullah A, Hochberg E. Primary effusion lymphoma. Oncologist 2007; 12:569–576. Review.

3. Simonelli C, Spina M, Cinelli R, Talamini R, Tedeschi R, Gloghini A, et al. Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol 2003; 21:3948–3954.

4. Brimo F, Michel RP, Khetani K, Auger M. Primary effusion lymphoma: a series of 4 cases and review of the literature with emphasis on cytomorphologic and immunocytochemical differential diagnosis. Cancer 2007; 111:224–233.

5. Valencia ME, Martinez P, Moreno V, Laguna F, Lahoz JG. AIDS-related body cavity-based lymphomas, herpesvirus-8 and HIV infection: a study of seven cases. AIDS 1999; 13:2603–2605.

6. Oksenhendler E, Clauvel JP, Jouveshomme S, Davi F, Mansour G. Complete remission of a primary effusion lymphoma with antiretroviral therapy. Am J Hematol 1998; 57:266.

7. Boulanger E, Gerard L, Gabarre J, Molina JM, Rapp C, Abino JF, et al. Prognostic factors and outcome of human herpesvirus 8-associated primary effusion lymphoma in patients with AIDS. J Clin Oncol 2005; 23:4372–4380.

8. Simonelli C, Tedeschi R, Gloghini A, Bortolin MT, Spina M, Bidoli E, et al. Characterization of immunologic and virological parameters in HIV-infected patients with primary effusion lymphoma during antiblastic therapy and highly active antiretroviral therapy. Clin Infect Dis 2005; 40:1022–1027.

9. Spina M, Gaidano G, Carbone A, Capello D, Tirelli U. Highly active antiretroviral therapy in human herpesvirus-8-related body-cavity-based lymphoma. AIDS 1998; 12:955–956.

10. Luppi M, Trovato R, Barozzi P, Vallisa D, Rossi G, Re A, Ravazzini L, et al. Treatment of herpesvirus associated primary effusion lymphoma with intracavity cidofovir. Leukemia 2005; 19:473–476.

11. Hocqueloux L, Agbalika F, Oksenhendler E, Molina JM. Long-term remission of an AIDS-related primary effusion lymphoma with antiviral therapy. AIDS 2001; 15:280–282.

12. Crum-Cianflone NF, Wallace MR, Looney D. Successful secondary prophylaxis for primary effusion lymphoma with human herpesvirus 8 therapy. AIDS 2006; 20:1567–1569.

13. Dupont C, Vasseur E, Beauchet A, Aegerter P, Berthe H, de Truchis P, et al. Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodeficience humaine. AIDS 2000; 14:987–993.

14. Ledergerber B, Telenti A, Egger M. Risk of HIV related Kaposi's sarcoma and non-Hodgkin's lymphoma with potent antiretroviral therapy: prospective cohort study. Swiss HIV Cohort Study. BMJ 1999; 319:23–24.

15. Polesel J, Clifford GM, Rickenbach M, Dal Maso L, Battegay M, Bouchardy C, et al. Swiss HIV Cohort Study. Non-Hodgkin lymphoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy. AIDS 2008; 22:301–306.

© 2008 Lippincott Williams & Wilkins, Inc.

Login