Abstract 11518: Long-Term Benefit of Intramuscular Transplantation of GCSF-Mobilized CD34+ Cells in No-Option Patients with Critical Limb Ischemia
Background: Our phase I/IIa clinical trial revealed that intramuscular transplantation of autologous, GCSF-mobilized CD34+ cells was safe, feasible and effective at week 4 and 12 post cellular therapy in 17 patients with chronic critical limb ischemia (CLI) in whom conventional revascularization was not indicated. However, long-term outcome of the stem/progenitor cell therapy has never been reported.
Methods: No-option patients with CLI by peripheral arterial disease (PAD) (N=5) or Buerger's disease (N=12) underwent leukoapheresis following 5-day subcutaneous infusion of GCSF (5-10 µg/kg/day). CD34+ cells were isolated from the apheresis product by a magnetic sorting system, CliniMACS®, then intramuscularly transplanted into ischemic lower limbs. Incidence of major clinical events and physiological parameters of limb ischemia were evaluated at year 1, 2, 3 and 4 post CD34+ cell transplantation.
Results: No patients died by year 1, whereas 3 patients with PAD died by year 3 and 1 patient with Buerger's disease died by year 4 due to cardiac complications. No patients underwent major amputation, whereas 1 patient with Buerger's disease underwent unplanned minor amputation by year 2. Non-CLI status (Rutherford's category ≤ 3) was achieved in 82% at year 1, 88% at year 2, 92% at year 3 and 85% at year 4 in all patients. Significant improvement of toe brachial pressure index (TBPI) was sustained up to year 4 vs baseline (0.44±0.28 vs 0.21±0.17, P=0.004) and that of transcutaneous partial oxygen pressure (TcPO2) was kept up to year 3 (52.1±12.5 vs 23.8±21.4, P=0.02). Ulcer size (5.7±18.0 vs 38.0±21.3 mm, P<0.0001), pain-free walking distance (895.3±219.4 vs 233.0±320.2 m, P<0.0001) and Wong Baker FACES pain rating scale (0.5±0.5 vs 2.4±0.7, P<0.0001), which were examined until year 1, significantly improved at year 1 compared with baseline. Subgroup analysis revealed the similar outcome in patients with Buerger's disease.
Conclusions: Favorable clinical outcomes as well as physiological evidences strongly indicate the long-term benefit of GCSF-mobilized CD34+ cell transplantation for retrieval from CLI, especially in patients with Buerger's disease. These promising results encourage a phase III, randomized clinical trial near future.
- © 2011 by American Heart Association, Inc.