Abstract 2192: Safety and Efficacy Is Sustained Up To One Year after Transplantation of Autologous CD34+ Cells in No-Option Patients with Chronic Critical Limb Ischemia
Background: We have started a single-blind and dose-escalation clinical trial regarding transplantation of autologous CD34+ cells (known to be enriched for endothelial progenitor cells) in patients with chronic critical limb ischemia (CLI).
Methods and Results: Patients with chronic CLI by peripheral vascular disease or Buerger disease, in whom Rutherford class was 4–6 and who were not eligible for bypass surgery and angioplasty, were enrolled. Each patient underwent single apheresis following 5-day subcutaneous infusion of G-CSF (10 μg/kg/day). Peripheral blood CD34+ cells, which were isolated from the apheresis product by a magnetic cell sorting system, were intramuscularly transplanted into a more severely ischemic leg of each patient under lumbar anesthesia. Cell dose for injection was 105 cells/kg in 6 patients (Lo group: 4 male, 58±9 yrs) and 5 x 105 cells/kg in 6 cases (Hi group: 3 male, 40±5 yrs). Safety and efficacy follow up was completed up to 1 year after the cell transplantation in both groups. No patients have experienced any severe adverse events such as death, MACE including myocardial/cerebral infarction and major amputation. In all patients, Wong-Baker pain rating scale in the treated legs was significantly reduced at wk 4, wk 12 and yr 1 compared with pre-treatment (pre, 2.5±0.2; wk 4, 1.3±0.3; wk 12, 0.8±0.3; yr 1, 0.6±0.1, P=0.006 at wk 4 and P<0.0001 at wk 12 and yr 1). Toe brachial pressure index (pre, 0.15±0.04; wk 4, 0.26±0.04; wk 12, 0.34±0.05; yr 1, 0.37±0.06, P=0.01 at wk 12 and P=0.003 at 1yr), transcutaneous partial oxygen pressure (pre, 10.2±3.4; wk 4, 24.5±6.5, wk 12, 41.4±5.7, yr 1, 47.5±6.1 mmHg, P=0.003 at wk 12 and P<0.0001 at 1 yr) and pain-free walking distance by treadmill (pre, 322.3±131.8; wk 4, 519.0±108.3; wk 12, 676.5±128.1; 1 yr, 891.9±80.3 m, P=0.04 at wk 12 and P=0.002 at yr 1) did not change at wk 4, however significantly increased at wk 12 and yr 1 compared with pre-treatment. All parameters were not significantly different between wk 4, wk 12 and yr1.
Conclusion: Outcome of the early stage trial suggests that mobilization, harvest and transplantation of autologous CD34+ cells may be feasible and safe in patients with CLI. The clinical effect observed by wk 4 or wk 12 was sustained up to 1 year following the cell transplantation.