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MULTICENTRIC CASTLEMAN'S DISEASE TREATED WITH COMBINATION CHEMOTHERAPY AND RITUXIMAB IN HIV-POSITIVE MEN
J Routy, A Bestawros, C Seguin, R Michel, M Boulassel
Objectives: Multicentric Castleman's disease (MCD) is a rare polyclonal lymphoproliferative condition that may develop in HIV-infected patients co-infected with herpesvirus-8 (HHV8). Therapy for MCD is not well established and includes: ART, corticosteroids, chemotherapies. Recently, anti-CD20 monoclonal antibody (Rituximab) as been shown to induce significant treatment response, however such a response may be only observed after several weeks. In order to obtain a rapid and long-lasting treatment response, we assessed the tolerance and efficacy of a combination of an immuno-chemotherapy.
Methods: The treatment included a single course of anthracycline-based chemotherapy with Rituximab (375 mg/m2 weekly × 4). Tumor size, development of other HHV-8 related disorders including Kaposi sarcoma (KS) and effusion lymphoma, albumin, CRP, LDH, CD4 cell count, and viral load for HHV-8 were used to assess treatment response.
Results: All four patients presented with severe constitutional symptoms, generalized lymph nodes and HHV-8 was detected in the tumor by LANA-1 immunostaining and in peripheral blood by PCR. The mean CD4 cell count was 183/mm3 and none had received ART at the time of MCD diagnosis. In all the cases, treatment was well tolerated and a swift clinical improvement was observed within 48 hours. MCD lesions did not recur after a mean follow-up of 32 months. However, KS lesions developed or recurred in three patients in spite of a HIV viral load below level of detection. These three patients responded well to liposomal anthracycline (Caelix) chemotherapy.
Conclusions: Our study suggests that the combination of anti-CD20 monoclonal antibody with a single course of chemotherapy may represent a valid strategy for the treatment of severe MCD. HHV8related disorders including MCD and KS respond to different types of chemotherapy regimens, suggesting an important insight into HHV8 pathogenesis. Further studies are warranted to assess the long-term efficacy and safety of such an approach.