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

      Abstract

      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/m2 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.

      Keywords

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      References

        • George J.
        Thrombotic thrombocytopenic purpura.
        New Engl J Med. 2006; 354: 1927-1935
        • Moake J.L.
        Journey in reverse: TTP from bedside to blood bank to bench.
        J Clin Apher. 2007; 22: 37-49
        • Rock G.A.
        • Shumak K.H.
        • Buskard N.A.
        • et al.
        Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group.
        N Engl J Med. 1991; 325: 393-397
        • Rock G.
        • Porta C.
        • Bobbio-Pallavicini E.
        Thrombotic thrombocytopenic purpura treatment in year 2000.
        Haematologica. 2000; 85: 410-419
        • Veyradier A.
        • Meyer D.
        Thrombotic thrombocytopenic purpura and its diagnosis.
        J Thromb Haem. 2005; 3: 2420-2427
        • Sadler J.
        Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura.
        Blood. 2008; 12: 11-18
        • Kappers-Klunne M.C.
        • Wijermans P.
        • Fijnheer R.
        • et al.
        Splenectomy for the treatment of thrombotic thrombocytopenic purpura.
        Br J Haematol. 2005; 130: 768-776
        • O’Connor N.T.
        • O’Shea M.J.
        • Hill L.F.
        Vincristine for thrombotic thrombocytopenic purpura [letter].
        Lancet. 1992; 340: 490
        • Durand J.M.
        • Lefevre P.
        • Kaplanski G.
        • et al.
        Vincristine for thrombotic thrombocytopenic purpura.
        Lancet. 1992; 340: 977-978
        • Durand J.M.
        • Lefevre P.
        • Kaplanski G.
        • et al.
        Ineffectiveness of high-dose intravenous gammaglobulin infusion in thrombotic thrombocytopenic purpura [letter].
        Am J Hematol. 1993; 42: 234
        • Udvardy M.
        • Rak K.
        Cyclophosphamide for chronic relapsing thrombotic thrombocytopenic purpura.
        Lancet. 1990; 336: 1508-1509
        • Crowther M.A.
        • Heddle N.
        • Hayward C.P.
        • et al.
        Splenectomy done during hematologic remission to prevent relapse in patients with thrombotic thrombocytopenic purpura.
        Ann Intern Med. 1996; 125: 294-296
        • Garvey B.
        Rituximab in the treatment of autoimmune haematological disorders.
        Br J Haematol. 2008; 141: 149-169
        • Fakhouri F.
        • Vernant J.P.
        • Veyradier A.
        • et al.
        Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases.
        Blood. 2005; 106: 1932-1937
        • Franchini M.
        • Veneri D.
        • Lippi G.
        • et al.
        The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders.
        Thromb Haem. 2006; 96: 119-125
        • Scully M.
        • Cohen H.
        • Cavenagh J.
        • et al.
        Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura following rituximab is associated with a reduction in IgG antibodies to ADAMTS-13.
        Br J Haematol. 2007; 136: 451-461
        • Del Río-Garma J.
        • Alvarez-Larrán A.
        • Martínez C.
        • et al.
        Methylene blue-photoinactivated plasma versus quarantine fresh frozen plasma in thrombotic thrombocytopenic purpura: a multicentric, prospective cohort study.
        Br J Haematol. 2008; 143: 39-45
        • Gray R.J.
        A class of K-sample test for comparing the cumulative incidence of competing risk.
        Ann Stat. 1988; 16: 1141-1154
        • George J.N.
        • Sadler J.E.
        • Lämmle B.
        Platelets: thrombotic thrombocytopenic purpura.
        Hematology (Am Soc Hematol Educ Program). 2002; : 315-334
        • Tsai H.M.
        Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura.
        J Am Soc Nephrol. 2003; 14: 1072-1081
        • Howard M.A.
        • Williams L.A.
        • Terrell D.R.
        • et al.
        Complications of plasma exchange in patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
        Transfusion. 2006; 46: 154-156
        • Gutterman L.A.
        • Kloster B.
        • Tsai H.M.
        Rituximab therapy for refractory thrombotic thrombocytopenic purpura.
        Blood Cells Mol Dis. 2002; 28: 385-391
        • Sadler J.E.
        • Moake J.L.
        • Miyata T.
        • et al.
        Recent advances in thrombotic thrombocytopenic purpura.
        Hematology (Am Soc Hematol Educ Program). 2004; : 407-423
        • Shumak K.H.
        • Rock G.A.
        • Nair R.C.
        Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Canadian Apheresis Group.
        Ann Intern Med. 1995; 122: 569-572
        • Ziman A.
        • Mitri M.
        • Klapper E.
        • et al.
        Combination vincristine and plasma exchange as initial therapy in patients with thrombotic thrombocytopenic purpura: one institution’s experience and review of the literature.
        Transfusion. 2005; 45: 41-49
        • Kremer Hovinga J.A.
        • Studt J.D.
        • Demarmels F.
        • et al.
        Splenectomy in relapsing and plasma-refractory acquired thrombotic thrombocytopenic purpura.
        Haematologica. 2004; 89: 320-324
        • Millward P.M.
        • Bandarenko N.
        • Chang P.P.
        • et al.
        Cardiogenic shock complicates successful treatment of refractory thrombotic thrombocytopenia purpura with rituximab.
        Transfusion. 2005; 45: 1481-1486