Combination Chemotherapy in Refractory Immune Thrombocytopenic Purpura

Figueroa, Michael L.; Gehlsen, Jane A.; Hammond, Denis B.; Ondreyco, Sharon M.; Piro, Lawrence D.; Pomeroy, Talisman; Williams, Frederick; McMillan, Robert

doi:10.1056/nejm199304293281703

Cited by 121 publications

(54 citation statements)

References 15 publications

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“…[2][3][4][5] Data in the literature suggest that intensive chemotherapy, particularly pulse cyclophosphamide, may produce better results by virtue of the suppression of lymphocyte numbers and function. 21,22 In our series, however, 4 patients had received pulse cyclophosphamide with no response. Besides, 2 of these patients had a complete and sustained response with rituximab, indicating either different immunologic targets or a greater efficacy of the antibody in eliminating autoreactive clones.…”

Section: Discussionmentioning

confidence: 69%

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

Stasi

Pagano

Stipa

et al. 2001

Blood

507

370

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The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m 2 once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 ؋ 10 9 /L) was observed in 5 cases, a partial response (platelet count between 50 and 100 ؋ 10 9 /L) in 5 cases, and a minor response (platelet count below 50 ؋ 10 9 /L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted. (Blood. 2001; 98:952-957)

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Section: Discussionmentioning

confidence: 69%

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

Stasi

Pagano

Stipa

et al. 2001

Blood

507

370

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“…24 In the 1980s and 90s, combination chemotherapy and subsequently IV cyclophosphamide alone were tried and had some success in "curing" ITP. [26][27][28] Once other options became available, e.g. dexamethasone [8][9][10][11][12] and rituximab, [15][16][17][18] the toxicity of cyclophosphamide relegated it to being a tertiary option.…”

Section: Discussionmentioning

confidence: 99%

Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration

et al. 2014

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Adults with newly diagnosed or persistent immunothrombocytopenia frequently relapse upon tapering steroids; adults and children with chronic disease have an even lower likelihood of lasting response. In adults with newlydiagnosed immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day x four days and 4 rituximab infusions were superior to dexamethasone alone. Studies have also shown three cycles of dexamethasone are better than one and patients with persistent/chronic immunothrombocytopenia respond less well to either dexamethasone or rituximab. Therefore, 375 mg/m 2 x 4 rituximab was combined with three 4-day cycles of 28 mg/m 2 (max. 40 mg) dexamethasone at 2-week intervals and explored in 67 ITP patients. Best long-term response was assessed as complete (platelet count ≥100x10 9 /L) or partial (50-99x10 9 /L). Only 5 patients had not been previously treated. Fifty achieved complete (n=43, 64%) or partial (n=7, 10%) responses. Thirty-five of 50 responders maintained treatment-free platelet counts over 50x10 9 /L at a median 17 months (range 4-67) projecting 44% eventfree survival. Duration of immunothrombocytopenia less than 24 months, achieving complete responses, and being female were associated with better long-term response (P<0.01). Adverse events were generally mild-moderate, but 3 patients developed serum sickness and 2 colitis; there were no sequelae. Dexamethasone could be difficult to tolerate. Fourteen patients became hypogammaglobulinemic and half had increased frequency of minor infections; 9 of 12 evaluable patients recovered their IgG levels. Rituximab combined with three cycles of dexamethasone provides apparently better results to reported findings with rituximab alone, dexamethasone alone, or the combination with one cycle of dexamethasone. The results suggest medical cure may be achievable in immunothrombocytopenia, especially in women and in patients within two years of diagnosis. (clinicaltrials.gov identifier:02050581) Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration

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“…6,7 In this report, we describe our experience using a combination of azathioprine, mycophenolate mofetil, and cyclosporine to treat patients with particularly severe and refractory ITP.…”

Section: Introductionmentioning

confidence: 99%

Combination immunosuppressant therapy for patients with chronic refractory immune thrombocytopenic purpura

Arnold

Nazi

Santos

et al. 2010

Blood

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Treatment options for patients with chronic refractory immune thrombocytopenic purpura (ITP) are limited. Because combination immunosuppressant therapy appeared to be effective in ITP and other disorders, we used this approach in patients with particularly severe and refractory ITP. In this retrospective, observational study, we determined the response (platelet count above 30 ؋ 10 9 /L and doubling of baseline) among 19 refractory ITP patients. Treatment consisted of azathioprine, mycophenolate mofetil, and cyclosporine. The patients had failed a median of 6 prior treatments, including splenectomy (in all except 1 IntroductionImmune thrombocytopenic purpura (ITP) is an acquired bleeding disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production. Patients with chronic refractory ITP have the highest risk of death and disease-related or therapy-related complications. 1,2 Treatment options include aggressive immunosuppressant therapy, and most recently thrombopoietin (TPO) receptor agonists. 3,4 Single-agent immunosuppressant drugs such as azathioprine and cyclosporine have been used to treat refractory patients with moderate success 5 ; however dose escalation can cause morbidity, and other options are needed.Over the past several decades, physicians have noted that greater efficacy can be achieved using a combination of unrelated but synergistic medications. 6,7 In this report, we describe our experience using a combination of azathioprine, mycophenolate mofetil, and cyclosporine to treat patients with particularly severe and refractory ITP. MethodsPatients in this report had a platelet count less than 20 ϫ 10 9 /L that persisted for at least 12 months with an inadequate or transient response to multiple therapies. The senior author (J.G.K.) offered the option of a combination of immunosuppressant therapy. Patients with comorbidities such as liver failure or uncontrolled hypertension were not offered this treatment. Institutional Review Board approval from McMaster University was obtained to retrospectively review the medical charts of all patients with ITP treated in our clinic; this report describes only those patients treated with combination immunosuppressant therapy. Institutional Review Board approval was not required for the administration of the combination of immunosuppressant agents (each on its own an accepted therapy for ITP 8 ), which was given per clinical need.Medical records of each patient were reviewed by 3 independent assessors and data were abstracted in triplicate and verified for consistency. Platelet count measurements and follow-up visits were done as per routine care and mean monthly platelet counts were calculated. Target doses of immunosuppressant medications were azathioprine 2 mg/kg per day; mycophenolate mofetil 1 to 2 g/d; and cyclosporine 2 mg/kg per day. Low-dose cyclosporine was chosen to minimize toxicity and avoid the need for drug level monitoring.We defined overall response as a platelet count level of 30 ϫ 10 9 /L or higher and do...

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Combination Chemotherapy in Refractory Immune Thrombocytopenic Purpura

Abstract: Combination chemotherapy is beneficial in some patients in whom immune thrombocytopenia is refractory to corticosteroids and splenectomy.

Cited by 121 publications

References 15 publications

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura

Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration

Combination immunosuppressant therapy for patients with chronic refractory immune thrombocytopenic purpura

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