Dapsone: An Old but Effective Therapy in Pediatric Refractory Immune Thrombocytopenia

Abstract

There are no definitive guidelines for management of chronic or refractory immune thrombocytopenia (ITP) in children. Dapsone is an inexpensive and efficacious, yet neglected, therapeutic option for treatment of chronic ITP. We evaluated the efficacy and safety of dapsone in the management of chronic ITP in children. Children with chronic ITP \ 14 years with minimum grade 2 bleeds refractory to either splenectomy/rituximab/ eltrombopag; who were offered dapsone therapy were retrospectively analyzed. Dapsone intolerance and G6PD deficiency were excluded. Dapsone was started at a dose of 1-2 mg/kg/day. Response to dapsone as per international working group definitions, time to response along with side-effects were noted. Forty-four children enrolled; 29 analyzed. Nineteen were refractory to rituximab, 8 to splenectomy and 6 to eltrombopag. Median age was 9.8 years (3-14) with 16/29 males. Median dapsone dose was 1.59 mg/kg/day (range 1-2.1). Overall response was seen in 21/29 (72%): Complete Response in 7/29 (24%), Partial Response in 14/29 (48%). All responses were sustained for minimum 3 months. Median duration to response was 2.9 months (2-6.6). Median follow up was 28 months (6-73) and relapse rate-21%. Major side effects noted: Methemoglobinemia-01, skin ulceration-02. In three cases dapsone could be tapered and stopped without relapse. Dapsone is an economical and efficacious agent with good safety profile in childhood chronic/refractory ITP.

Pediatric Refractory Immune Thrombocytopenia: a Systematic Review

“…Of note, some studies' definition of rITP was contingent on patients having undergone splenectomy. 8,9,11,14 Current ASH guidelines list splenectomy as a deferred treatment option after other treatment options have been attempted. 1 Therefore, requiring that the patient failed prior splenectomy is not an appropriate criteria for children with ITP.…”

“…One study's rITP definition included: "unable or disinclined to undergo splenectomy and in whom primary objective is to improve health related quality of life was used ". 8 Treatment in Patients with Refractory ITP Eight out of 11 studies discussed the treatment for pediatric patients with rITP. Treatment modalities included splenectomy 9,11 , rituximab 9,13,[16][17][18] , romiplostim 14 , and dapsone 8 (Table 2).…”

Advances in management of pediatric chronic immune thrombocytopenia: a narrative review

“…Dapsone has a response rate of 50% to 72%, a complete response of 20% to 48%, and a partial response of 17% to 48% [50][51][52]. The duration to response is approximately 1 to 3 months, and the relapse rate is approximately 10% to 20%.…”

“…As well-known hematologic adverse effects, methemoglobinemia and hemolysis occur in 10% to 20% of cases. Rarely, agranulocytosis and aplastic anemia may also occur, and characteristic hypersensitivity reactions such as fever, eosinophilia, and skin rash may occur with dapsone [50][51][52].…”

Immune thrombocytopenia

“…Platelet count starts improving after 3-4 weeks with an overall response rate of 30-60%. ITP patients who have already undergone splenectomy show inferior response to dapsone (Provan et al, 2019;Copper et al, 2019;VancineCalifani et al, 2008;Khera et al, 2020 ). Common side effects include gastrointestinal discomfort, headache, insomnia, methemoglobinemia, and hemolytic anemia in men with G6PD deficiency .…”