Combined Chelation Therapy with Daily Oral Deferiprone and Twice-Weekly Subcutaneous Infusion of Desferrioxamine in Children with β-Thalassemia: 3-Year Experience

Abstract

Objective: To study the efficacy of combined treatment with oral and subcutaneous iron chelators. Material and Methods: 50-100 mg/kg/day of oral deferiprone (DFP) combined with 40 mg/kg/dose s.c. desferrioxamine (DFO) twice weekly were given to transfusion-dependent β-thalassemia children. Results: Enrolled patients (9 with β-thalassemia major and 33 with β-thalassemia hemoglobin E), ranging from 3 to 18 years in age, were divided into 3 groups; group 1 ferritin ≥1,000-2,500 ng/ml (n = 10), group 2 ferritin >2,500-4,000 ng/ml (n = 23) and group 3 ferritin >4,000 ng/ml (n = 9). Of the 42 patients, 28 reached the 36-month follow-up. Ten patients whose ferritin declined <15% while receiving 100 mg/kg/day of DFP were considered nonresponders. The median age and previous transfusion duration before enrollment were significantly higher in nonresponders than responders (p = 0.04 and 0.003, respectively). The responders exhibited a significant fall in median ferritin levels from 2,954.6 to 936.6 ng/ml (p < 0.001). Time to a significant decrease in serum ferritin among responders was 6 months. In 13 patients, 16 episodes of adverse events occurred: hemophagocytosis with cytopenia (n = 1), neutropenia (n = 2), thrombocytopenia (n = 2), elevated alanine aminotransferase (n = 5), elevated serum creatinine (n = 1), proteinuria (n = 1) and gastrointestinal discomfort (n = 4). Conclusion: Combination therapy with daily oral DFP and subcutaneous DFO twice weekly is a safe and effective alternative to chelation monotherapy in β-thalassemia children. © 2014 S. Karger AG, Basel

Efficient attenuation of Friedreich's ataxia (FRDA) cardiomyopathy by modulation of iron homeostasis-human induced pluripotent stem cell (hiPSC) as a drug screening platform for FRDA

“…Furthermore, slight supplementation of iron may be beneficial to treatment because iron deficiency would worsen the disease progression due to more aggressive uptake of iron by a false signal sense in disease condition [36,44]. Our results were also agreed with clinical studies with the cohort of thalassemia patients treated with oral DFP undergoing less myocardial iron burden and better global systolic ventricular function comparing with the patients treated with the other two types of iron chelator oral deferasirox or subcutaneous desferrioxamine [31,32,35]. This could be explained by the fact that the iron chelator, DFP, is able to enter mitochondria and redirect iron to other cell compartment.…”

“…To address the iron misdistribution with enhanced iron concentrations in mitochondria and relative cytosolic labile iron depletion, the use of membrane-permeable iron chelators, for example, deferiprone, has been considered [29,30]. This drug has been widely used for oral prescription of the treatment of beta-thalassemia [31][32][33][34][35]. Deferiprone was tested in a pilot, open-label study and in a randomized, placebocontrolled phase II clinical trial.…”

Single-center retrospective study of the effectiveness and toxicity of the oral iron chelating drugs deferiprone and deferasirox

“…Deferiprone is frequently prescribed as first line therapy even to children (for example, 68.3% of children in the Middle East [32], despite inadequate monitoring [33–35]). Its recommendation in pediatric practice persists despite higher rates of toxicity in children, including neutropenia (12.6%), agranulocytosis (5%) [35], and liver dysfunction [36, 37]), than were reported in the Apotex-directed “safety” study [34].…”

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

“…The important problems related to chronic Fe-overload observed in thalassemia patients can be overcome using chelating agents such as deferiprone, deferasirox, and deferoxamine [32]. Recently, combined treatment with oral deferiprone and subcutaneous desferoxamine twice weekly was shown to be a safe and effective alternative to chelation monotherapy in transfusion-dependent beta-thalassemia children [33]. The use of combined Fe chelators to prevent Fe-overload cardiomyopathy in thalassemia has been reported [34, 35].…”