Refractory autoimmune thrombocytopenic purpura: Responses to treatment with a recombinant antibody to lymphocyte membrane antigen CD20 (rituximab)

Narang, Mohit; Penner, John A.; Williams, Dan

doi:10.1002/ajh.10413

Cited by 24 publications

(14 citation statements)

References 14 publications

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“…Most patients will sustain a hemostatic response after splenectomy, although relapses can occur at any time [8] . Refractory idiopathic thrombocytopenic purpura represents a life-threatening condition that fails to respond to a variety of therapeutic measures [9] . In recent years, immunosuppressive agents such as cyclosporine A and MMF were used to treat refractory ITP as second line drugs.…”

Section: Discussionmentioning

confidence: 99%

“…The therapeutic effects were found to be better in male patients than female patients. 9 /L) over 6 months, unrelated to any underlying viral infection, collagen vascular diseases, malignancy, or medications; (2) without or with slight splenomegaly, with a normal or increased number of megakaryocytes in bone marrow, and no failure of maturing; (3) the failure of drug treatment and surgery treatment (prednisone, vincristine, danazol, long-term use of traditional Chinese medicine or intravenous injection of high doses of immunoglobulin G and splenectomy) ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

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Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura

Zhang

Cao

et al. 2005

Acta Pharmacol Sin

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Aim: To determine whether mycophenolate mofetil (MMF) has beneficial effects on refractory idiopathic thrombocytopenic purpura (ITP) and the corresponding cellular mechanism. Methods: Twenty refractory ITP patients resistant to corticosteroid and/or splenectomy and chemical therapy were given MMF 1.5‐2.0 g/d orally for a 2 to 4‐month period. Serum immunoglobulin was detected by rate nephelometry. Platelet‐associated antibodies (PAIgG) were assayed by enzymelinked immunosorbant assay. The immunophenotypic analysis was performed on a flow cytometer and cell apoptosis was detected with transferase mediated dUTP biotin nick end labeling (TUNEL) method. Results: Sixteen of the 20 (80%) patients had responses to MMF treatment; 9 (45%) achieved a complete response, 4 (20%) achieved a partial response, and 3 (15%) achieved a minor response. The therapeutic effects were found to be better in male patients than female patients. The number of CD3+ peripheral blood cells (PBCs) and CD4+ PBCs increased and the number of CD8+ PBCs decreased. The plasma level of IgG, IgM, IgA and platelet associated IgG (PAIgG) decreased in 86% of the patients. TUNEL assay showed that mycophenolate acid (MPA) 0.1 mmol/L induced apoptosis of peripheral blood mononuclear cells isolated from refractory ITP patients. The apoptosis rate was increased in male patients after treatment with MPA, but was unchanged in female patients. Conclusion: Therapy for a period of 8 to 16 weeks with mediandose of MMF was valuable for the treatment of refractory ITP.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura

Zhang

Cao

et al. 2005

Acta Pharmacol Sin

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“…Rituximab, a chimeric anti-CD20 monoclonal antibody, causes a rapid depletion of B cells [9]. Although rituximab was originally introduced for the treatment of malignant lymphomas [10,11], several recent studies have shown that rituximab may also be effective in the treatment of ITP and other autoimmune diseases [12,19,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]. The current results of all published case reports and clinical trials using rituximab in the treatment of immune thrombocytopenias have most recently been reported showing an overall response rate of about 50% [34].…”

Section: Introductionmentioning

confidence: 99%

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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“…PAIg levels, however, did not correspond to platelet count responses in three of the patients studied [20]. Although pretreatment levels of PAIgG antibodies were significantly increased in six of these patients, only one of the responders displayed a posttreatment decline in these autoantibody levels [107].…”

Section: Laboratory Resultsmentioning

confidence: 99%

“…Different targeted immunotherapies have been explored in chronic refractory ITP, such as anti-CD20, anti-CD154 and anti-CD52 antibodies [19][20][21]. This review will summarize the therapeutic mechanisms and clinical results of rituximab, a chimeric anti-CD20 monoclonal antibody, in the treatment of chronic ITP.…”

Section: Introductionmentioning

confidence: 99%

Rituximab treatment for chronic refractory idiopathic thrombocytopenic purpura

Zhou

Yang

2008

Critical Reviews in Oncology/Hematology

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Refractory autoimmune thrombocytopenic purpura: Responses to treatment with a recombinant antibody to lymphocyte membrane antigen CD20 (rituximab)

Cited by 24 publications

References 14 publications

Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura

Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura

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

Rituximab treatment for chronic refractory idiopathic thrombocytopenic purpura

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