Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura

Stasi, Roberto; Stipa, Elisa; Forte, Vittorio; Meo, Paola; Amadori, Sergio

doi:10.1182/blood-2002-02-0392

Cited by 101 publications

(76 citation statements)

References 2 publications

(3 reference statements)

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“…The present study has confirmed the observation in a previous study of two response patterns, an early response occurring within 1-2 weeks after the first rituximab infusion and a late response with a rise in the platelet count several weeks after ending rituximab therapy [18,25]. In our series, it was not possible to characterize further those patients with an early response as compared to patients with a late response.…”

Section: Discussionsupporting

confidence: 91%

Rituximab chimeric anti‐CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

et al. 2005

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Idiopathic thrombocytopenic purpura is an autoimmune disease which involves opsonization of platelets by autoantibodies directed against different surface glycoproteins, leading to their premature destruction by the reticuloendothelial system. Management of patients with refractory ITP is difficult. Recent studies have shown that rituximab, a chimeric anti‐CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results of a retrospective Danish multicenter study of rituximab in the treatment of adult patients with refractory ITP. Thirty‐five patients (median age 52 years, range 17–82 years, 17 males) were included. One patient had immune thrombocytopenia and neutropenia. All patients had received prednisolone (Pred). Next to Pred, 25 patients had been treated with high‐dose IgG, and in 16 patients a splenectomy had been performed. Sixteen patients had been treated with azathioprine. Other treatments included, e.g., cyclosporine, danazol, cyclophosphamide, vincristine, interferon, and dexamethasone. The patients were treated with a dose regimen of 375 mg/m2 i.v. approximately once weekly for 4 consecutive weeks. Six patients received a fixed dose of 500 mg disregarding their weight supplemented by 100 mg of methylprednisone i.v. or 50–100 mg of Pred given as premedication together with an antihistamine just before infusion of rituximab. The large majority of patients also received Pred and, in some cases, other concomitant immunosuppressive treatment during part of their rituximab treatment. A complete response (CR) was defined as a rise in the platelet count > 100 × 109/L, a partial response (PR) as a rise in the platelet count > 50 × 109/L, and a minor response (MR) as a rise in the platelet count < 50 × 109/L. No response (NR) was defined as no increase in the platelet count. Because 4 patients were treated twice, a total of 39 outcomes of rituximab treatment were evaluated. Rituximab proved to be effective in 17 of 39 treatments [overall response 44% with 7 CR (18%) (1 patient showed a CR twice), 6 PR (15%), and 4 MR (10%)]. In 9/13 cases of CR or PR, the response (platelet level > 50 × 109/L) was prompt, 1–2 weeks after the first infusion. The remaining patients responded 3–8 weeks later. Patients with CR and PR have been in remission for a median of 47 weeks. In general the side effects were few. In 2 cases, the treatment was stopped because of side effects either during or after the first infusion. Two fatal outcomes were recorded. A 71‐year‐old female with severe lung disease died 6 days after the first infusion of respiratory failure. The other patient, a 73‐year‐old man also with severe chronic obstructive lung disease, died of pneumonia approximately 13 weeks following the last rituximab treatment. It is concluded that rituximab may be a useful alternative therapy in patients with severe and symptomatic ITP refractory to conventional treatment. Am. J. Hematol. 78:275–280, 2005. © 2005 Wiley‐Liss, Inc.

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Section: Discussionsupporting

confidence: 91%

Rituximab chimeric anti‐CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

et al. 2005

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“…Several patients had reductions to subnormal levels in their serum IgG, IgM, or both. In general, the infusions were well tolerated in these studies of ITP patients, since no major toxic effects and only minor infusion-related fevers and chills were reported (23,24).…”

Section: Rituximab For Autoimmune Thrombocytopeniamentioning

confidence: 90%

“…In another study, 25 adult patients with chronic ITP who had demonstrated resistance to conventional treatment regimens received the full 4-week regimen of rituximab at 375 mg/m 2 (24). Of these 25 patients, 5 had increases in their platelet counts to Ͼ100,000/mm 3 , and 5 had increases in their platelet counts to the range of 50,000-100,000/mm 3 .…”

Section: Rituximab For Autoimmune Thrombocytopeniamentioning

confidence: 99%

Rituximab therapy and autoimmune disorders: Prospects for anti–B cell therapy

Silverman¹,

Weisman²

2003

Arthritis & Rheumatism

343

204

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“…They hypothesized that, as rituximab-opsonized B cells will be recognized by monocytes and macrophages, these effector cells would be diverted away from interactions with autoimmune antibody complexes. A similar theory was put forward by Stasi et al (2002) to explain the very rapid effect of rituximab treatment in some patients with idiopathic thrombocytopenic purpura (ITP). Although the pathogenesis of ITP is autoantibody-mediated, immunoglobulin (Ig)G autoantibodies are driven by T cell-dependent mechanisms and many reports have described several consistent T-cell abnormalities in ITP (Coopamah et al, 2003).…”

Section: The Mechanism Of Action Of Rituximabmentioning

confidence: 99%

Rituximab in the treatment of autoimmune haematological disorders

2008

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SummaryCurrent treatment regimens for haematological autoimmune diseases are relatively non-selective and are often associated with considerable toxicity. Recently, it has become clear that B cells play a key role in both the development and perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with autoimmune diseases. This article reviews data supporting the use of rituximab -an anti-CD20 monoclonal antibody that specifically depletes B cells -in four key autoimmune haematological disorders: idiopathic thrombocytopenic purpura (ITP); autoimmune haemolytic anaemia (AIHA); acquired haemophilia; and thrombotic thrombocytopenic purpura (TTP). Although treatment of ITP, AIHA, acquired haemophilia and TTP with rituximab is still relatively uncommon, results from case series and small phase II trials indicate that patients of all ages can respond to rituximab, irrespective of the number or type of prior treatments that they have received. Moreover, patients with these diseases receiving rituximab experienced predominantly mild adverse events, with only a few serious adverse events reported. These data suggest that rituximab provides an effective and well-tolerated alternative treatment option for patients with ITP, AIHA, acquired haemophilia and TTP, many of whom have limited treatment choices.

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Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura

Cited by 101 publications

References 2 publications

Rituximab chimeric anti‐CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

Rituximab chimeric anti‐CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

Rituximab therapy and autoimmune disorders: Prospects for anti–B cell therapy

Rituximab in the treatment of autoimmune haematological disorders

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