Department of Pediatric Hematology, Ain Shams University, Children's Hospital, Cairo, Egypt.
Research Center, Cairo University, Cairo, Egypt.
Am J Hematol. 2023 Sep;98(9):1415-1424. doi: 10.1002/ajh.27010. Epub 2023 Jul 4.
Children with transfusion-dependent thalassemia (TDT) require regular blood transfusions that, without iron-chelation therapy, lead to iron-overload toxicities. Current practice delays chelation therapy (late-start) until reaching iron overload (serum ferritin ≥1000 μg/L) to minimize risks of iron-depletion. Deferiprone's distinct pharmacological properties, including iron-shuttling to transferrin, may reduce risks of iron depletion during mild-to-moderate iron loads and iron overload/toxicity in children with TDT. The early-start deferiprone (START) study evaluated the efficacy/safety of early-start deferiprone in infants/young children with TDT. Sixty-four infants/children recently diagnosed with beta-thalassemia and serum ferritin (SF) between 200 and 600 μg/L were randomly assigned 1:1 to receive deferiprone or placebo for 12 months or until reaching SF-threshold (≥1000 μg/L at two consecutive visits). Deferiprone was initiated at 25 mg/kg/day and increased to 50 mg/kg/day; some recipients' dosages increased to 75 mg/kg/day based on iron levels. The primary endpoint was the proportion of patients ≥SF-threshold by month 12. Monthly transferrin saturation (TSAT) assessment evaluated iron-shuttling. At baseline, there was no significant difference in mean age (deferiprone: 3.03 years, placebo: 2.63 years), SF (deferiprone: 513.8 μg/L, placebo: 451.7 μg/L), or TSAT (deferiprone: 47.98%, placebo: 43.43%) between groups. At month 12, there was no significant difference in growth or adverse event (AE) rates between groups. No deferiprone-treated patients were iron-depleted. At month 12, 66% of patients receiving deferiprone remained below SF threshold versus 39% of placebo (p = .045). Deferiprone-treated patients showed higher TSAT levels and reached ≥60% TSAT threshold faster. Early-start deferiprone was well-tolerated, not associated with iron depletion, and efficacious in reducing iron overload in infants/children with TDT. TSAT results provide the first clinical evidence of deferiprone shuttling iron to transferrin.
患有输血依赖型地中海贫血症（TDT）的儿童需要定期输血，如果不进行铁螯合治疗，会导致铁过载毒性。目前的治疗方法是延迟螯合治疗（起始较晚），直到出现铁过载（血清铁蛋白≥1000μg/L），以最大程度地降低缺铁的风险。地拉罗司具有独特的药理学特性，包括将铁转运到转铁蛋白，这可能会降低在轻度至中度铁负荷和 TDT 儿童的铁过载/毒性期间发生缺铁的风险。早期起始地拉罗司（START）研究评估了早期起始地拉罗司在 TDT 婴儿/幼儿中的疗效/安全性。64 名最近被诊断为β-地中海贫血且血清铁蛋白（SF）在 200 至 600μg/L 之间的婴儿/儿童被随机分配 1:1 接受地拉罗司或安慰剂治疗 12 个月或直至达到 SF 阈值（两次连续就诊时≥1000μg/L）。地拉罗司起始剂量为 25mg/kg/天，然后增加至 50mg/kg/天；根据铁水平，一些患者的剂量增加至 75mg/kg/天。主要终点是在第 12 个月时达到 SF 阈值的患者比例。每月转铁蛋白饱和度（TSAT）评估评估铁转运。在基线时，两组之间的平均年龄（地拉罗司：3.03 岁，安慰剂：2.63 岁）、SF（地拉罗司：513.8μg/L，安慰剂：451.7μg/L）或 TSAT（地拉罗司：47.98%，安慰剂：43.43%）无显著差异。在第 12 个月时，两组之间的生长或不良事件（AE）发生率无显著差异。没有接受地拉罗司治疗的患者出现缺铁。在第 12 个月时，66%接受地拉罗司治疗的患者仍低于 SF 阈值，而安慰剂组为 39%（p=0.045）。地拉罗司治疗组的 TSAT 水平更高，达到≥60%TSAT 阈值的速度更快。早期起始地拉罗司耐受性良好，与缺铁无关，可有效降低 TDT 婴儿/儿童的铁过载。TSAT 结果提供了地拉罗司将铁转运到转铁蛋白的首个临床证据。
