Division of Hematology, The Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA.
Department of Pediatrics, School of Medicine, Cairo University, Cairo, Egypt.
Blood Adv. 2022 Feb 22;6(4):1243-1254. doi: 10.1182/bloodadvances.2021004938.
Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.
许多患有镰状细胞病（SCD）或其他贫血症的患者需要接受慢性输血治疗，这往往会导致铁过载，需要螯合治疗。铁螯合剂地拉罗司常用于地中海贫血综合征患者，但 SCD 患者的数据有限。这项开放标签研究评估了地拉罗司在接受慢性输血治疗的 SCD 或其他贫血患者中的疗效和安全性。共有 228 名患者（平均年龄：16.9[范围，3-59]岁；46.9%为女性）被随机分为接受口服地拉罗司（n=152）或皮下去铁胺（n=76）治疗。主要终点是 12 个月时肝脏铁浓度（LIC）的基线变化，通过 R2磁共振成像（MRI）评估。地拉罗司的 LIC 最小二乘均值（标准误差）变化为-4.04（0.48）mg/g 干重，而去铁胺为-4.45（0.57）mg/g 干重，协方差分析显示地拉罗司不劣于去铁胺（最小二乘均值差异 0.40[0.56]；96.01%置信区间，-0.76 至 1.57）。地拉罗司在心脏 T2MRI 和血清铁蛋白方面也显示出不劣效性。两组的总不良事件（AE）、与治疗相关的 AE、严重 AE 和导致停药的 AE 发生率无显著差异。与地拉罗司治疗相关的 AE 包括腹痛（17.1%的患者）、呕吐（14.5%）、发热（9.2%）、丙氨酸转氨酶（9.2%）和天冬氨酸转氨酶水平升高（9.2%）、中性粒细胞减少症（2.6%）和粒细胞缺乏症（0.7%）。地拉罗司的疗效和安全性特征是可以接受的，与依赖输血的地中海贫血患者所见一致。这项试验研究在 www://clinicaltrials.gov 上注册为 #NCT02041299。
