Combined chemotherapy including high‐dose methotrexate in KSHV/HHV8‐associated primary effusion lymphoma

Abstract

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade nonHodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected homosexual men with severe immunosuppression and other KSHV/HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis is poor with a median survival of less than 6 months in most cohorts. The achievement of a sustained complete remission is rare. High-dose chemotherapy regimens are warranted to improve complete remission rate and survival. Seven patients with AIDS-associated PEL were treated with a combined chemotherapy including high-dose methotrexate followed by leucovorin rescue. In all cases, KSHV/HHV8 sequences were detected in the effusion samples using quantitative PCR assays. Five patients had a pre-existing KS, associated in three cases with multicentric Castleman's disease (MCD). Upon diagnosis, 6 patients received antiretroviral therapy, which was maintained during chemotherapy in 5 of them. At time of analysis, 3 out of 7 patients were in complete remission 18, 26, and 78 months after PEL diagnosis. Three patients died with a progressive PEL at 22, 67, and 153 days after diagnosis, and 1 patient died 9 months after PEL diagnosis with a MCD-associated plasmablastic NHL. Complete remission was obtained in 3 out of 7 patients treated for AIDS-associated PEL with combined chemotherapy containing high-dose methotrexate. Am.

How I treat HIV-associated lymphoma

“…Other approaches, such as high-dose methotrexate and parenteral zidovudine with interferon-␣, have been studied but have demonstrated limited efficacy. 82,83 The prognosis of plasmablastic lymphoma in the setting of HIV has also been historically poor. 38,84 The impact of CART has not been well studied but anecdotal reports suggest its prognosis may have improved since the introduction of CART.…”

Primary Effusion Lymphoma

“…Much like other NHLs, combination chemotherapy forms the backbone of therapy for PEL, and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimens are considered first-line therapy [1,56]. In one series, modified CHOP-like regimens were able to achieve a 43% complete remission rate [1], whereas highdose methotrexate was added to CHOP-like regimens in another report showing a similar rate of success [57]. We would caution against the use of high-dose methotrexate, especially in the initial cycles, given the accumulation of methotrexate in effusions with resultant delayed clearance and the increased risk for systemic toxicity [58].…”

KSHV/HHV8‐associated lymphomas

“…The suggested benefit of high-dose methotrexate (Boulanger et al, 2003) in association with CHOP (cyclophosphamide, doxorubicin, prednisone, vincristine)-like regimens is negatively balanced by the hampered toxicity of methotrexate in the presence of serous effusions (Boulanger et al, 2005).…”

“…The inhibition of viral replication and a direct pro-apoptotic effect on lymphoma cells by the high concentration of cidofovir achieved through the intracavitary administration probably explain this relevant clinical effect. Intracavitary cidofovir, as well as interferon-a (Boulanger et al, 2003), may represent a reasonable choice in patients refractory to conventional chemotherapy or in elderly patients not eligible to more toxic systemic therapies.…”