Effect of Treatment with Rituximab in Patients with Refractory Autoimmune Cytopenias.

Abstract

The autoimmune cytopenias encompass the disorders of immune thrombocytopenia purpura (ITP), autoimmune haemolytic anaemia (AIHA), autoimmune neutropenia (AIN), pure red cell aplasia (PRCA) and various combinations of these conditions. We describe 34 patients with severe autoimmune cytopenias resistant to standard immunosuppression treated with the anti-CD20 monoclonal antibody Rituximab. 17 patients had ITP, 6 AIN, 2 AIHA, 2 PRCA, 4 AIHA and ITP (Evan's syndrome), 1 AIHA and AIN, 1 PRCA and ITP, and 1 AIN and ITP. 28 patients had primary autoimmune cytopenias and in 6 patients, the cytopenia was secondary to an underlying disorder (3 B-NHL, 1 T-NHL, 1 B-CLL and 1 SLE).Rituximab was administered intravenously at a dose of 375mg/m2 weekly for 4 weeks. 33 of 34 patients completed treatment. In one patient treatment was discontinued after 3 infusions due to a hypotensive syncopal episode. No other major infusion related side effects were observed. Responses were seen in 9/17 patients with ITP, 2/2 patients with AIHA and 4/4 patients with AIHA and ITP. Responses were sustained in 8/9 ITP patients with median follow up of 25.8months (range 4–66 months). We observed a complete response in 5 of 7 ITP patients who were previously splenectomised.In contrast, there was no response in 5/6 patients with AIN and in 3/3 patients with PRCA.In two patients we observed severe neutropenia at 3 months post Rituximab which was associated with fatal infection in both patients, namely pnemocystis pneumoniae infection and acute exacerbation of bronchiectasis. Apart from these 2 cases no other infections were seen.In conclusion, Rituximab appears to be a an alternative and safe option in the treatment of patients with ITP, AIHA and Evan's syndrome inducing sustained clinical remissions in patients who have failed to respond to conventional immunosuppression and/or splenectomy. In contrast Rituximab does not seem to be effective in AIN and PRCA and this may reflect a different pathogenesis for these conditions.