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  • Title: B-cell compartment as the selective target for the treatment of immune thrombocytopenias.
    Author: Zaja F, Vianelli N, Sperotto A, De Vita S, Iacona I, Zaccaria A, Masolini P, Tomadini V, Tani M, Molinari AL, Baccarani M, Fanin R.
    Journal: Haematologica; 2003 May; 88(5):538-46. PubMed ID: 12745273.
    Abstract:
    BACKGROUND AND OBJECTIVES: Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells. Treatment with rituximab is associated with the development of a severe (even if transient) B-cell depletion from peripheral blood and lymphatic tissues. These effects could be useful in autoimmune diseases in order to interfere with the production of pathologic antibodies. DESIGN AND METHODS: To investigate this, we treated 20 patients with rituximab 375 mg/m2 i.v. every 7 days for 4 times. These 20 patients all had active and symptomatic autoimmune thrombocytopenia that had relapsed or was refractory to standard therapies (15 had idiopathic thrombocytopenic purpura, 1 idiopathic thrombocytopenia and neutropenia, 2 thrombocytopenia and concomitant undifferentiated connective tissue disease, and 2 had thrombocytopenia and concomitant B-cell lymphoprolipherative disorders). Only treatment with steroids, if strictly necessary to maintain a safe number of platelets, was allowed during the period of rituximab administration, but only patients who reached steroid discontinuation (previously not possible) were considered responders. RESULTS: Treatment was well tolerated and no acute or delayed toxic events were recorded. Rituximab proved to be active in 13/20 patients, with 9 complete and 4 partial responses. In 10/13 (77%) the response (platelet level > 50x10(9)/L) was prompt, being achieved already after the first of the four planned infusions. After a median follow-up of 180 days (range: 60-480) 4 patients had relapsed. Age < or = 60 years was correlated with a better response rate (p=0.03). No correlation was observed between response and gender, time from diagnosis to treatment (< 12 vs > 12 months), total and CD20+ lymphocyte count, level of CD20 expression on B cells before the therapy and pharmacokinetics of the drug. INTERPRETATION AND CONCLUSIONS: Rituximab appears to be a promising immunotherapeutic agent for the treatment of autoimmune thrombocytopenias.
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