Using Rituximab Plus Fludarabine and Cyclophosphamide as a Treatment for Refractory Mixed Cryoglobulinemia Associated With Lymphoma




Treatment of refractory mixed cryoglobulinemia (MC) with severe organ involvement remains challenging. Fludarabine, cyclophosphamide, and rituximab (FCR) treatment is highly effective for patients with chronic lymphocytic leukemia and marginal-zone lymphoma. We first report the safety and efficacy of FCR treatment in severe and refractory MC vasculitis associated with lymphoma.


We report the safety and efficacy of fludarabine (40 mg/m2 orally on days 2–4), cyclophosphamide (250 mg/m2 orally on days 2–4), and rituximab (375 mg/m2 on day 1), every 4 weeks, for 3 to 6 cycles in 7 consecutive patients with severe and refractory MC.


Clinical features of MC included purpura (n = 7), polyneuropathy (n = 6), and kidney (n = 4) and cardiac involvement (n = 2). Previous treatment included rituximab (n = 5), corticosteroids (n = 5), antiviral therapy (n = 5), cyclophosphamide (n = 3), and plasmapheresis (n = 2). All patients achieved clinical response, with 3 patients (42.9%) achieving a complete remission and 4 patients (57.1%) a partial remission. Cryoglobulin decreased from 0.94 to 0.41 gm/liter (P = 0.015). After a followup of 27 months, 2 patients experienced a relapse of MC. Five patients (71.4%) experienced side effects, including cytopenia (n = 5), pneumopathy (n = 2), and serum sickness (n = 1).


The FCR regimen represents an effective treatment in severe and refractory MC.