Long-term clinical outcome after intramuscular transplantation of granulocyte colony stimulating factor-mobilized CD34 positive cells in patients with critical limb ischemia.

Abstract

BACKGROUND:

Our phase I/IIa clinical trial revealed that intramuscular transplantation of autologous, GCSF-mobilized CD34+ cells was safe, feasible and potentially effective at week 4 and 12 post cellular therapy in 17 patients with chronic critical limb ischemia (CLI) (5 patients with atherosclerotic peripheral arterial disease (PAD) and 12 with Buerger's disease). However, long-term outcome of the cell therapy has yet to be reported.

METHODS AND RESULTS:

Incidence of major clinical events and physiological parameters of limb ischemia were evaluated at week 52, 104, 156 and 208 post CD34+ cell therapy. No patients died by week 104, whereas 3 patients with PAD died by week 156 and 1 patient with Buerger's disease died by week 208 due to cardiac complications. No patients underwent major amputation, whereas 1 patient with Buerger's disease underwent unplanned minor amputation by week 104. CLI-free ratio was 88.2% at week 52 and 104, 92.3% at week 156 and 84.6% at week 208 in all patients. Significant improvement of toe brachial pressure index versus baseline was sustained up to week 208 and that of transcutaneous partial oxygen pressure was kept up to week 156. The Wong-Baker FACES pain rating scale, ulcer size and exercise tolerance significantly improved at week 52, the final evaluation time point, 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.

• Authors: Makoto Kinoshita, Yasuyuki Fujita, Minako Katayama, Rie Baba, Maki Shibakawa, Kimiko Yoshikawa, Nobuyuki Katakami, Yutaka Furukawa, Tomio Tsukie, Tohru Nagano, Yasuo Kurimoto, Kazuo Yamasaki, Nobuhiro Handa, Yukikatsu Okada, Kaori Kuronaka, Yukiko Nagata, Yoshihiro Matsubara, Masanori Fukushima, Takayuki Asahara, Atsuhiko Kawamoto
• Journal: Atherosclerosis (Atherosclerosis) Vol. 224 Issue 2 Pg. 440-5 (Oct 2012) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 22877866 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antigens, CD34
• Biomarkers
• Granulocyte Colony-Stimulating Factor

Topics

• Adult
• Aged
• Amputation, Surgical
• Antigens, CD34 (analysis)
• Biomarkers (analysis)
• Chronic Disease
• Critical Illness
• Disease-Free Survival
• Endothelial Cells (drug effects, metabolism, transplantation)
• Female
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Injections, Intramuscular
• Ischemia (diagnosis, etiology, mortality, physiopathology, surgery)
• Japan
• Limb Salvage
• Linear Models
• Lower Extremity (blood supply)
• Male
• Middle Aged
• Peripheral Arterial Disease (complications, diagnosis, mortality, physiopathology, surgery)
• Recovery of Function
• Reoperation
• Stem Cell Transplantation (adverse effects, mortality)
• Survival Analysis
• Thromboangiitis Obliterans (complications, diagnosis, mortality, physiopathology, surgery)
• Time Factors
• Transplantation, Autologous
• Treatment Outcome
• Young Adult