Complete remission and virologic response to combined chemoimmunotherapy (R-CVP) followed by rituximab maintenance in HIV-negative, HHV-8 positive patient with multicentric Castleman disease

A 78-year-old man was hospitalised in our Medical Unit in September 2006 because of fatigue, dyspnoea, weight loss, itching and fever for 1 month. The physical examination revealed paleness, mild hepatomegaly and splenomegaly (4 cm below the costal margin) but no peripheral lymphoadenopathy. The peripheral blood showed normocytic anemia (Hb, 7.4 g/dL; WBC, 6.456 10/L; MCV, 86 fL; PLT, 100 6 10/L; reticulocytes, 2%; neutrophils, 59%; lymphocytes, 29%; monocytes, 10%; eosinophils, 1%), elevated ESR (125 mm in 1 h) and CRP (2.8 mg/dL), hyperglobulinemia (total protein, 8.1 g/dL; albumin, 2.2 g/dL; gammaglobulins, 4.2 g/dL). Laboratory findings were the following: creatinine, 1.2 mg/dL; uric acid, 7.3 mg/dL; LDH, 200 UI/L; cholesterol, 85 mg/dL; bilirubin, 0.6 mg/ dL; GOT, 13 U/L; GPT, 17 U/L; iron, 23 mg/dL; ferritin, 1027 mg/L; serum erythropoietin (S-EPO), 17.5 mU/mL; b2 microglobulin, 11.8 mg/L. Haptoglobin, serum B12 and RBC folate levels were normal. Immunoelectrophoresis showed a monoclonal IgG kappa (IgG, 4230 mg/dL; IgA, 52 mg/dL; IgM, 105 mg/dL) without Bence Jones proteinuria. The patient had a positive Coombs test with the evidence of cryoagglutinins; antinuclear antibody (ANA titer 1:320) and the rheuma test were positive with low complement (C3,C4) serum levels. WidalWright and serological tests for EBV, CMV, Leishmania, HBV, HCV and HIV were negative. Lymphocyte immunophenotyping on peripheral blood by flow cytometric analysis revealed the following values: CD3, 81%; CD4, 36%; CD8, 36%; CD20, 17%; CD38, 31%; kappa chain, 47%; lambda chain, 52%. The bone marrow aspiration showed 22% erythroid cells, 64% myeloid cells with mild eosinophilia, 7% lymphocytes and 7% plasma cells. On X-ray examination osteolytic lesions were not found; a CT scan of the thorax and abdomen revealed splenomegaly, enlarged mediastinal and retroperitoneal lymph nodes and mild pleural, peritoneal and pericardial effusion. Amyloid deposits cannot be identified histologically by Congo red staining with abdominal fat biopsy. After supportive treatment and low dose steroids lasting 2 months, the patient was re-examined; on physical examination was not febrile but he had splenomegaly and diffuse peripheral lymphoadenopathy. CT scan revealed enlarged laterocevical and supraclavicular lymph nodes and increase in size of the mediastinal and sub-diaphragmatic nodes. The peripheral blood confirmed anemia (Hb, 9.9 g/dL) and increased hyperglobulinemia (total protein, 9 g/dL; albumin, 2.5 g/dL; gammaglobulins, 5 g/dL). These clinical findings suggested a multicentric Castleman disease (MCD). PCR Real Time assay has been performed on serum and peripheral blood mononuclear cells (PBMCs) to research human herpesvirus 8 (HHV-8) DNA. DNA extraction from serum and peripheral