Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases

Godeau, Bertrand; Durand, J.M.; Roudot‐Thoraval, Françoise; Tennezé, Anne; Oksenhendler, Éric; Kaplanski, Gilles; Schaeffer, A; Bierling, Philippe

doi:10.1046/j.1365-2141.1997.412687.x

Cited by 82 publications

(85 citation statements)

References 9 publications

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“…Intensive consolidation chemotherapy for acute myeloid leukemia (AML) patients in complete remission is being increasingly administered on an outpatient basis. Although this approach has been found to be safe and feasible in younger patients [1][2][3][4][5][6], its safety in older patients remains unknown. We therefore undertook an evaluation of outpatient-based consolidation chemotherapy in older AML patients, and compared results to younger patients treated at the same institution over the same time period.…”

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confidence: 99%

“…This agent is contraindicated in patients with G6PD deficiency and has a good safety profile. Hemolytic anemia and an increase of methemoglobin (MHb) are the main reported side effects [8,9].Previous studies highlighted the therapeutic activity of dapsone as salvage therapy in primary ITP with 40-60% overall response rate and 15-50% CR rate [1][2][3][4][5][6]. The response to dapsone was unaffected by pretreatment characteristics such as sex, age, platelet count, or duration of ITP and was generally treatment dependent, even if the persistence of response after dapsone discontinuation has been registered in some patients.…”

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Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab

et al. 2011

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Dapsone is an antibacterial sulfonamide with anti-inflammatory property, which showed therapeutic activity in patients with immune thrombocytopenia (ITP) [1][2][3][4][5][6]; the activity in patients who showed refractoriness to rituximab is unknown. We evaluated the effect of dapsone in 20 consecutive adult patients, median age 51 years, with primary ITP previously treated at least with steroids and rituximab. Median baseline platelet count was 19 3 10 9 /L, and the median interval between diagnosis of ITP and dapsone therapy was 46 months. Response (platelet count 30 3 10 9 /L) and complete response (CR; platelet count 100 3 10 9 /L) were 55 and 20%, respectively; median time to response (TTR) was 1 month. All responders were able to interrupt any other specific anti-ITP treatment. The median duration of dapsone therapy in responders and the median response duration were 31 and 42 months, respectively. None of responders lost response during treatment. One patient in CR interrupted dapsone after 9 months and still maintained the response after 48 months. None of the patients interrupted the treatment for toxicity. All the patients were screened for normal glucose-6-phosphate-dehydrogenase (G6PD); two patients showed mild increase of methemoglobin (MHb). These results highlight the therapeutic activity and good safety profile of dapsone in patients with ITP who previously failed rituximab treatment. ITP is an acquired autoimmune disease characterized by increased platelet destruction, impaired megakaryocyte maturation with reduced platelet production, and possible hemorrhagic complications. Treatment is generally indicated for symptomatic patients, that is, those with active bleeding or very low platelet count (usually < 20-30 3 10 9 /L). Glucocorticoids, potentially associated with intravenous high-dose immunoglobulin in those cases with high risk of major bleeding, represent the standard first line of treatment [7]. However, despite the high initial therapeutic efficacy, in most cases, steroids tapering or withdrawal is followed by a drop in platelet count and the need for additional treatment. Treatment of patients with relapsed or refractory symptomatic ITP, particularly of those who are not eligible for, refused or failed splenectomy, still lacks a gold standard therapy. Dapsone is an antibacterial sulfonamide synthesized in 1908 with antimicrobial effect against leprosy, pneumocystic Jiroveci pneumonia in AIDS, toxoplamosis, and malaria. Since 1950s, dapsone also was recognized to have activity in a number of noninfectious inflammatory diseases of the skin as dermatitis herpetiformis and blistering disorders. The anti-inflammatory effect of dapsone is not fully understood, but it appears at least targeted against neutrophils, with interference of myeloperoxidase, inhibition of lysosomal enzymes, chemotaxis, and integrin-mediated adherence function. This agent is contraindicated in patients with G6PD deficiency and has a good safety profile. Hemolytic anemia and an increase of methemoglobin (MHb) are the ma...

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Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab

et al. 2011

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“…Its use is based on prospective and retrospective cohort studies. [59][60][61] In one of the largest series, 66 patients with chronic ITP were treated with oral dapsone at a dose of 75 to 100 mg. A platelet count .50 3 10 9 /L was achieved in 33 patients (50%), 20 of whom continued to respond for a median duration of 12.5 months. 59 In a literature review of dapsone, overall response rates ranged from 40% to 75%.…”

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confidence: 99%

“…[59][60][61] In one of the largest series, 66 patients with chronic ITP were treated with oral dapsone at a dose of 75 to 100 mg. A platelet count .50 3 10 9 /L was achieved in 33 patients (50%), 20 of whom continued to respond for a median duration of 12.5 months. 59 In a literature review of dapsone, overall response rates ranged from 40% to 75%. 62 Toxicities of dapsone include methemoglobinemia, agranulocytosis, aplastic anemia, hypersensitivity, gastrointestinal complications, and hemolysis in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency.…”

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confidence: 99%

How I treat refractory immune thrombocytopenia

Cuker

Neunert

2016

Blood

123

129

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This article summarizes our approach to the management of children and adults with primary immune thrombocytopenia (ITP) who do not respond to, cannot tolerate, or are unwilling to undergo splenectomy. We begin with a critical reassessment of the diagnosis and a deliberate attempt to exclude nonautoimmune causes of thrombocytopenia and secondary ITP. For patients in whom the diagnosis is affirmed, we consider observation without treatment.Observation is appropriate for most asymptomatic patients with a platelet count of 20 to 30 3 10 9 /L or higher. We use a tiered approach to treat patients who require therapy to increase the platelet count. Tier 1 options (rituximab, thrombopoietin receptor agonists, low-dose corticosteroids) have a relatively favorable therapeutic index. We exhaust all Tier 1 options before proceeding to Tier 2, which comprises a host of immunosuppressive agents with relatively lower response rates and/or greater toxicity. We often prescribe Tier 2 drugs not alone but in combination with a Tier 1 or a second Tier 2 drug with a different mechanism of action. We reserve Tier 3 strategies, which are of uncertain benefit and/or high toxicity with little supporting evidence, for the rare patient with serious bleeding who does not respond to Tier 1 and Tier 2 therapies. (Blood. 2016;128(12): 1547-1554 Case 1A 10-year-old male was diagnosed with primary immune thrombocytopenia (ITP) 5 months ago when he presented with epistaxis, petechiae, bruising, and a platelet count of 5 3 10 9 /L. He responded transiently to intravenous immunoglobulin G (IgG), but epistaxis recurred 2 weeks later. He subsequently received a short course of oral corticosteroids to which he had a temporary response in platelet count and cessation of epistaxis. Since discontinuing corticosteroids, he has had only occasional bruising and petechiae. His platelet count is currently 13 3 10 9 /L. He states that ITP is not interfering with activities.

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Lack of relevance of the acetylator status on dapsone response in chronic autoimmune thrombocytopenic purpura

Louët

Ruivart²,

Bierling

et al. 1999

Am. J. Hematol.

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Dapsone provides an alternative treatment for patients with chronic autoimmune thrombocytopenic purpura (AITP) who had inadequate response to conventional therapy. However, the efficacy of this treatment is achieved in only 50% of patients. Dapsone is partly metabolized by the polymorphic N-acetyltransferase 2% and 50% of Caucasian patients show a genetically determined slow acetylator phenotype. The aim of our study was to investigate the influence of the acetylator status on dapsone efficacy in patients with chronic AITP. Nineteen caucasian adults with chronic AITP, previously treated by dapsone, were included in the study. Acetylator phenotype was determined by using a caffeine urinary test. Among the fourteen fast acetylator patients, eight patients exhibited positive response to dapsone and six patients did not. Among the five slow acetylator patients, one patient displayed a positive response to dapsone. Comparison of data by using the Fisher's exact test did not reach statistical significance. Our results do not support a relationship between dapsone efficacy and acetylator status in adults with chronic AITP. Am. J. Hematol. 62:251-252, 1999.

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Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases

Cited by 82 publications

References 9 publications

Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab

Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab

How I treat refractory immune thrombocytopenia

Lack of relevance of the acetylator status on dapsone response in chronic autoimmune thrombocytopenic purpura

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