Treatment lines of childhood chronic ITP: A retrospective single-center analysis

Abstract

Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children. Approximately 20–25% of children develop a chronic course of the disease. Many treatment options are available, including chronic use of first-line therapies, e.g., corticosteroids, intravenous immunoglobulin or anti-Rh-D, and second-line therapies, including dexamethasone, high-dose methylprednisolone, intensive immunosuppressants, rituximab, thrombopoietin receptor agonists (TPO-RAs), splenectomy, and many others; however, none of these treatments have been determined to be the best. In this study, we retrospectively reviewed the course, response to different treatment lines and outcome of children with chronic ITP over a period of ten years to compare the efficacy of different treatment options, aiming to determine a scale of priority for selecting the most costeffective treatment. A retrospective study was conducted and included children diagnosed with chronic ITP from January 2008 until December 2018 who were followed at the Pediatric Hematology Unit of Mansoura University Children Hospital, Mansoura, Egypt. The study proposal was approved on February 14, 2017 (approval No 17.02.59) by the Institutional Review Board (IRB) of the Faculty of Medicine, Mansoura University, Egypt. All research steps were conducted according to the Declaration of Helsinki. The diagnosis of chronic ITP was based upon the persistence of thrombocytopenia lasting for more than 1 year with or without therapy. Bone marrow aspiration was performed for all patients to confirm the diagnosis of chronic ITP and exclude other causes of thrombocytopenia. Data relevant to chronic ITP patients diagnosed from 2008 to 2018 were retrieved from the Electronic Data System of Hospital Management of Mansoura University Children Hospital, including age, sex, diagnosis date, duration of chronicity, treatment given during the chronic phase and response. Treatment regimen was immune modulatory therapies (high-dose dexamethasone, IV rituximab or low-dose dexamethasone + azathioprine), thrombopoietin receptor agonists (TPO-RAs) (eltrombopag or romiplostim). Out of 405 newly diagnosed ITP patients in a period of 10 years in our center, 103 progressed to chronic disease, of whom 29 were lost to follow-up, while 74 patients were followed at the hematology outpatient clinic and enrolled in the current study (32 males and 42 females, median age – 10 years, median initial platelet count – 16 × 109 /l). Approximately one-third of patients (25~33.8%) were managed conservatively; of them, 19 patients achieved sustained remission, and 6 patients needed another treatment line. Forty-six (62%) patients received immunomodulatory therapies. Twentyeight patients (37.8%) were treated with TPO-RAs. No differences were observed between the 3 types of immunomodulatory therapies regarding relapse-free survival and duration of remission (р value: 0.7). Additionally, no differences were noted according to relapse-free survival among those treated with eltrombopag and romiplostim (р value: 0.7). The number of male children who had a sustained response was significantly higher than that of female children among patients receiving immunomodulatory therapies (71.4% vs 28.6%, respectively) (р value 0.01). There were significantly more patients on TPO-RA with a sustained response than patients on immune modulators, and consequently, the number of patients who relapsed on immunomodulators was higher than that of those on TPO-RA (67.9% vs 30.4% compared to 69.9% vs 32.1%, р value 0.01). Many of our patients who received immunomodulators and failed to achieve or lost a response before 2015 were switched to TPO-RAs with comparable efficacy apart from sustainability, which was in favor of the latter. Additionally, among the types of immunomodulators, rituximab did not show superior efficacy compared to other types, with lower costs for the latter, leading to the abandonment of its use, particularly in limited resource countries such as ours.