Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study.

BACKGROUND: Between 30% and 60% of patients with thrombotic thrombocytopenic purpura (TTP) relapse and mortality remains at 15-20%. Limited clinical data suggest that the administration of anti-CD20 antibody (rituximab) may be useful in preventing acute refractory and chronic relapsing TTP. DESIGN AND METHODS: We studied the clinical response to rituximab in 24 adult patients (median age 42 years, range 24-72 years) from 15 Spanish centers with an acute refractory (14 patients) or acute relapsing (10 patients) episode of idiopathic TTP. On admission, every patient received daily plasma exchange (PE). Rituximab was administered at a dose of 375 mg/m(2) weekly for a median of 13 days (range 0-57 days) after starting PE for a median of 4 doses (range 1-8 doses). RESULTS: No severe acute or delayed toxicity was observed in the patients treated with rituximab. Three (12.5%) patients died because of TTP-related causes. The remaining 21 (87.5%) patients achieved complete remission in a median of 21 days (range 2-35 days) after initiating rituximab. After a median follow-up of 30 months (range 7.5-74 months), 18 patients are in remission and 3 patients have relapsed at 7, 29, and 29 months. CONCLUSIONS: Rituximab appears to be a safe, effective therapy and has a high response rate for the treatment of acute refractory or relapsing idiopathic TTP in adult patients.

Treatment with megestrol acetate improves human immunodeficiency virus-associated immune thrombocytopenia.

Splenic macrophage Fc gamma receptors participate in the pathophysiology of immune cytopenias, and in such disorders, the beneficial effects of glucocorticoids are in part mediated by decreased expression of macrophage Fc gamma receptors. In the animal model, progesterones, like glucocorticoids, inhibit expression of these receptors. Megestrol acetate (MA) is a progesterone frequently used for treating human immunodeficiency virus (HIV)-associated anorexia-cachexia. Twenty-eight patients with HIV-associated thrombocytopenia with shortened platelet survival and increased platelet-associated immunoglobulin G (IgG) who were being treated with MA for anorexia-cachexia were prospectively studied for a 6-month period to assess the potential role of progesterones in the treatment of immune thrombocytopenia. Treatment with MA for non-consecutive periods of 2 months and 1 month significantly increased platelet count and platelet survival without significant alteration of platelet-associated immunoglobulin levels. Of the 28 patients studied, 22 presented a complete response, 19 presented a complete response 1 month after finishing the MA treatment regimen, and 12 remained in complete response for a further month. Expression of Fc gamma receptors (Fc gamma RI and Fc gamma RII) by peripheral blood monocytes and the in vitro recognition of IgG-sensitized cells by monocytes were significantly decreased by the MA treatment. Decreased expression and functioning of these receptors significantly correlated with platelet counts and survival times, but no relationship was found with platelet-associated immunoglobulin, circulating immune complexes, body mass index, plasma HIV load, or CD4 lymphocyte levels. These results suggest that treatment with progesterones, like MA, may be an alternative therapy for immune cytopenias, with few side effects.