Safety and efficacy of early start of iron chelation therapy with deferiprone in young children newly diagnosed with transfusion‐dependent thalassemia: A randomized controlled trial

Abstract

Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion-dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants (N = 64 their age ranged from 10 to 18 (median 12) months, 54.7% males; receiving ≤6 transfusions; serum ferittin (SF) >400 to < 1000 ng/mL were randomized to "early start deferiprone" (.ES-DFP) at a low dose (50 mg/kg/day) or to "delay chelation" (DC), and remained in the study until their serum ferritin (SF) level reached ≥1000 μg/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months postrandomization, 100% of the subjects in DC group had achieved SF > 1000 µg/L and TSAT > 70% compared with none in the ES-DFP group. LPI level > 0.6 µM was observed in 97% vs. 40% of the DS and ES groups, respectively, (P < 0.001). The time to reach SF > 1000 µg/L was delayed by 6 months in the ES-DFP group (P < 0.001) without escalating DFP dose. No unexpected, serious, or severe adverse events were seen in the ES-DFP group.

The Course of Hepatitis C Infection and Response to Anti-Viral Therapy in Patients With Thalassemia Major and Hepatitis C Infection: A Longitudinal, Prospective Study.

“…In Egypt, as in several Mediterranean countries, β-thalassemia represents a major health problem since it constitutes 85% of hereditary hemoglobinopathies. The injurious impact of iron overload on the liver is further accentuated by the high prevalence of HCV infection among patients with thalassemia 17,18,19. Before the adoption of obligatory screening for HCV at blood banks in Egypt, the prevalence of HCV among multitransfused thalassemic patients reached almost 85% 20,21.…”

The History of Deferiprone (L1) and the Complete Treatment of Iron Overload in Thalassaemia

“…[120][121][122][123] Similar considerations are in progress regarding other clinical issues such as the early initiation of chelation therapy using L1 in thalassaemia children from about one year of age and also the initiation of combination therapies. [124][125][126][127] There are different criteria and opinions regarding the latter, with the ICOC L1/DF combination, for example, to be available, safe and flexible in all the patient categories and cases depending on the iron load levels and the rate of body iron intake from transfusions, whereas for other groups of investigators different restrictions are imposed in the use of combination protocols (Figure 6). 9,57,58,73,[81][82][83]99,100,103,128 The academic debates on the efficacy, toxicity, historical, and other aspects of L1, DF and DFRA and their combinations are likely to continue in the forthcoming years.…”

How I manage children with Diamond‐Blackfan anaemia

“…Alternatively, if MRI is not available or applicable, serum ferritin levels of ≥1000 lg/l and/or transferrin saturation levels ≥75% have been used as a starting point for chelation therapy. While chelating drugs are not registered yet for children younger than 2 years old (deferiprone <6 years), results of recent studies in younger children with transfusion-related iron overload are promising (Roggero et al, 2009;Berdoukas et al, 2013;Marsella & Borgna-Pignatti, 2014;Origa et al, 2016;Bellanti et al, 2017;Taher & Saliba, 2017;Elalfy et al, 2018).…”