Department of Pediatrics, Dr Balabhai Nanavati Hospital, Mumbai, India.
Indian Pediatr. 2012 Apr;49(4):281-5. doi: 10.1007/s13312-012-0042-4. Epub 2011 Aug 15.
To assess the efficacy of deferasirox as an iron chelator, with specific reference to reducing cardiac iron overload.
Prospective, open label, single arm study between 2008-2010. SETUP: Thalassemia center at a teaching hospital.
30 multitransfused Thalassemia Major (TM) patients receiving deferasirox (DFX) therapy.
All patients had MRI T2evaluation for cardiac iron load before starting DFX therapy. MRI T2 was performed on a 1.5 tesla Siemens sonata machine using thalassemia tools software and the ejection fraction measured using standard cardiac magnetic resonance sequence. Quantification of cardiac iron deposit was categorized into T2* <10 ms as high cardiac risk, 10-20 ms as intermediate risk, and >20 ms as low risk. We also estimated left ventricular ejection fraction (LVEF), end systolic volume (ESV) and end diastolic volume (EDV) using standard sequence. EF <56 % was considered to be significant cardiac dysfunction. DFX was administered in an initial dose of 20mg/kg/day and increased to a maximum of 35mg/kg/day. Serum ferritin level was estimated in pretransfusion samples at 1-3 monthly intervals. The primary end point of the study was change in serum ferritin level and cardiac MRI T2* value after 12-18 months therapy.
Of the 30 patients, cardiac iron value of >20 ms was seen in 15 (50%), whereas 9 (30%; ) had 20-10 ms, and 6 (20%) had <10 ms. The mean serum ferritin pre DFX therapy of all cases was 3859.8 ± 1690.70 ng/mL (1066 - 6725 ng/mL) and mean cardiac T2* was 23.8 ± 15.2 ms (6.24-69.2 ms). After 12 to 18 months of DFX therapy on a mean dose of 33 mg/kg/day, the mean serum ferritin was 2693.4 ± 1831.5 ng/mL (drop by 30.2%, P<0.001) and mean cardiac T2* was 24.2 ± 12.9 ms (increase of 1.6 %, P=0.87). Percentage change in cardiac iron was greater in high risk (24.8%) and intermediate risk (33.4%) patients than low risk patients (8.4%), though these values were not statistically significant. LVEF was 62.0 (± 7.0%) before treatment and changed to 58.9 (± 4.8%) after 18 months of therapy but the values remained within normal range and this change was not significant (P=0.061). Adverse effect of DFX included diarrhea, maculopapular skin rash and transient proteinuria that necessitated temporary stoppage of medication.
Deferasirox monotherapy has a good safety profile and effectively chelates total body iron. It is also a good myocardial iron chelator, more efficacious in moderate to severe cardiac iron overloaded patients.
评估地拉罗司作为铁螯合剂的疗效，特别是在降低心脏铁过载方面。
2008 年至 2010 年进行的前瞻性、开放标签、单臂研究。
教学医院的地中海贫血中心。
30 名接受地拉罗司（DFX）治疗的多发性输血地中海贫血症患者。
所有患者在开始 DFX 治疗前均进行心脏铁负荷的 MRI T2评估。使用地中海贫血工具软件在 1.5 特斯拉西门子奏鸣曲机上进行 MRI T2，并使用标准心脏磁共振序列测量射血分数。心脏铁沉积物的定量分类为 T2*<10ms 为高心脏风险，10-20ms 为中风险，>20ms 为低风险。我们还使用标准序列估计左心室射血分数（LVEF）、收缩末期容积（ESV）和舒张末期容积（EDV）。EF<56%被认为是显著的心脏功能障碍。DFX 的初始剂量为 20mg/kg/天，最大剂量为 35mg/kg/天。在 1-3 个月的间隔时间内，在输血前样本中估计血清铁蛋白水平。该研究的主要终点是 12-18 个月治疗后血清铁蛋白水平和心脏 MRI T2*值的变化。
在 30 名患者中，15 名（50%）患者的心脏铁值>20ms，9 名（30%）患者的心脏铁值为 20-10ms，6 名（20%）患者的心脏铁值<10ms。所有病例的血清铁蛋白治疗前平均值为 3859.8±1690.70ng/mL（1066-6725ng/mL），平均心脏 T2为 23.8±15.2ms（6.24-69.2ms）。在接受 33mg/kg/天的平均剂量 DFX 治疗 12-18 个月后，血清铁蛋白平均值为 2693.4±1831.5ng/mL（下降 30.2%，P<0.001），平均心脏 T2为 24.2±12.9ms（增加 1.6%，P=0.87）。高危（24.8%）和中危（33.4%）患者心脏铁的百分比变化大于低危患者（8.4%），尽管这些值没有统计学意义。DFX 治疗前 LVEF 为 62.0（±7.0%），治疗 18 个月后降至 58.9（±4.8%），但仍在正常范围内，这一变化无统计学意义（P=0.061）。DFX 的不良反应包括腹泻、斑丘疹性皮疹和短暂性蛋白尿，需要暂时停止用药。
地拉罗司单药治疗具有良好的安全性，并能有效螯合体内铁。它也是一种有效的心肌铁螯合剂，对中重度心脏铁过载患者更有效。
