A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia.
A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia.
复制标题
DOI：
10.1161/circinterventions.112.968321
复制
发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Autologous CD34+ Cell Therapy for Critical Limb Ischemia Investigators
中科院分区：
文献类型：
--
作者：
Losordo DW;Kibbe MR;Mendelsohn F;Marston W;Driver VR;Sharafuddin M;Teodorescu V;Wiechmann BN;Thompson C;Kraiss L;Carman T;Dohad S;Huang P;Junge CE;Story K;Weistroffer T;Thorne TM;Millay M;Runyon JP;Schainfeld R;Autologous CD34+ Cell Therapy for Critical Limb Ischemia Investigators
严重的肢体缺血(CLI)预示着在诊断的一年内有25%-35%的重大截肢风险。临床前研究表明，肌肉注射自体CD34+细胞可以改善肢体血流，降低截肢风险。在这项随机、双盲、安慰剂对照的初步研究中，我们评估了肌肉注射自体CD34+细胞的安全性和有效性，这些受试者患有中高危CLI，但不适合手术或经皮血管重建术(ACT34-CLI)。28名CLI患者随机接受治疗：7~1×105(低剂量)和9~1×106(高剂量)自体CD34+细胞/kg；12名安慰剂(对照组)。肌肉注射分布在缺血肢体内的8个部位。在注射后6个月，67%的对照组受试者经历了严重或轻微的截肢，而低剂量组和高剂量组的受试者分别为43%和22%(P=0.137)。这一趋势在12个月时继续，75%的对照组受试者经历过截肢，而低剂量组的43%和高剂量组的22%(P=0.058)。联合细胞治疗组的截肢发生率低于对照组(6个月：P=0.125；12个月：P=0.054)，低剂量组和高剂量组分别在6个月和12个月时显示出改善无截肢生存率的趋势。没有与细胞给药相关的不良安全信号。这项研究提供了证据，证明肌肉注射自体CD34+细胞在该患者群体中是安全的。与对照组相比，细胞处理组的截肢率有降低的有利趋势。这些发现值得在后期临床试验中进一步探索。
Critical limb ischemia (CLI) portends a risk of major amputation of 25-35% within 1 year of diagnosis. Pre-clinical studies provide evidence that intramuscular injection of autologous CD34+ cells improve limb perfusion and reduce amputation risk. In this randomized, double-blind, placebo-controlled pilot study, we evaluated the safety and efficacy of intramuscular injections of autologous CD34+ cells in subjects with moderate or high-risk CLI who were poor or non-candidates for surgical or percutaneous revascularization (ACT34-CLI). Twenty-eight CLI subjects were randomized and treated: 7 to 1×105 (low-dose) and 9 to 1×106 (high-dose) autologous CD34+ cells/kg; 12 to placebo (control). Intramuscular injections were distributed into 8 sites within the ischemic lower extremity. At 6 months post-injection 67% of control subjects experienced a major or minor amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.137). This trend continued at 12 months with 75% of control subjects experiencing any amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.058). Amputation incidence was lower in the combined cell-treated groups compared with control group (6 months: P=0.125; 12 months: P=0.054), with the low-dose and high-dose groups individually showing trends towards improved amputation free survival at 6 and 12 months. No adverse safety signal was associated with cell administration. This study provides evidence that intramuscular administration of autologous CD34+ cells was safe in this patient population. Favorable trends toward reduced amputation rates in cell-treated versus control subjects were observed. These findings warrant further exploration in later phase clinical trials.