Autologous Bone Marrow Mononuclear Cell Implantation and Its Impact on the Outcome of Patients With Critical Limb Ischemia　― Results of a Randomized, Double-Blind, Placebo-Controlled Trial ―

Abstract

Background: Cell therapy is a therapeutic option for patients presenting with nonrevascularizable critical limb ischemia (CLI). However there is a lack of firm evidence on its efficacy because of the paucity of randomized controlled trials. Methods and Results:The BALI trial was a multicenter, randomized, controlled, double-blind clinical trial that included 38 patients. For all of them, 500 mL of bone marrow were collected for preparation of a BM-MNC product that was implanted in patients assigned to active treatment. For the placebo group, a placebo cell-free product was implanted. Within 6 months after inclusion, major amputations had to be performed in 5 of the 19 placebo-treated patients and in 3 of the 17 BM-MNC-treated patients. According to a classical logistic regression analysis there was no significant difference. However, when using the jackknife analysis, 6 months after inclusion BM-MNC implantation was associated with a lower risk of major amputation (odds ratio (OR): 0.55; 95% confidence interval (CI): 0.52-0.58; P<0.0001) and of occurrence of any event (major or minor amputation, or revascularization) (OR: 0.30; 95% CI: 0.29-0.31; P<0.0001). The secondary endpoints (i.e., pain, ulcers, TcPO2, and ankle-brachial index value) were not statistically different between groups. Conclusions:Our results suggested that cell therapy reduced the risk of major amputation in patients presenting with nonrevascularizable CLI.

Impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia

“…The benefit of cell therapy on limb salvage has been proven by several randomized controlled trials and meta‐analyses in those with and without diabetes . These studies showed lower amputation rates in the cell therapy groups compared to standard treatment or placebo, while no significant differences in pain scores and ischaemic variables were observed in the study by Pignon et al .…”

“…The benefit of cell therapy on limb salvage has been proven by several randomized controlled trials [14,22,23] and metaanalyses in those with and without diabetes [24,25]. These studies showed lower amputation rates in the cell therapy groups compared to standard treatment or placebo, while no significant differences in pain scores and ischaemic variables were observed in the study by Pignon et al [23] in people who underwent bone marrow autograft for limb ischaemia. The outcomes of that trial were contrary to the results of most of the other published trials (including the present study), which reported improved ischaemic variables [18].…”

Impact of Therapeutic Angiogenesis Using Autologous Bone Marrow-Derived Mononuclear Cells Implantation in Critical Limb Ischemia With Scleroderma ― Subanalysis of the Long-Term Clinical Outcomes Survey ―

“…12,13 Randomized studies have reported that this cell therapy could lead to significant improvements in limb ischemia, thus extending amputation-free intervals and survival rates. 14,15 Moreover, Kondo et al reported a very long-term clinical outcome survey of BM-MNC implantation in no-option CLI patients, and indicated that BM-MNC implantation may be feasible and safe in CLI patients, particularly those with TAO and CD-associated vasculitis (CDV). 16 SSc is the most common cause of CLI among all patients with CD.…”

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia ― The SCELTA Trial ―

“…patients treated; however, treatment with autologous PB MNCs after G-CSF mobilization has been demonstrated to be safe by previous studies. 10,11,14, 15 A placebo control group was not envisaged in the present study because many studies have already demonstrated the efficacy of BM-MNC implantation; 14,27-33,43 these data were recently confirmed by Pignon et al, 47 who demonstrated the efficacy of BM-derived MNCs in reducing the frequency of major amputations in CLI patients in a randomized double-blind placebo-controlled trial. Thus, in the present study we considered the BM-MNC arm as the control condition, in accordance with the decision of the Ethics Committee.…”