Purified CD34+ cells versus peripheral blood mononuclear cells in the treatment of angiitis-induced no-option critical limb ischaemia: 12-Month results of a prospective randomised single-blinded non-inferiority trialResearch in context
Zhihui Dong,
Tianyue Pan,
Yuan Fang,
Zheng Wei,
Shiyang Gu,
Gang Fang,
Yifan Liu,
Yang Luo,
Hao Liu,
Tiejun Zhang,
Meiyu Hu,
Daqiao Guo,
Xin Xu,
Bin Chen,
Junhao Jiang,
Jue Yang,
Zhenyu Shi,
Ting Zhu,
Yun Shi,
Peng Liu,
Weiguo Fu
Affiliations
Zhihui Dong
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China; Corresponding authors at: Department of Vascular Surgery of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Tianyue Pan
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Yuan Fang
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Zheng Wei
Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
Shiyang Gu
Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
Gang Fang
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Yifan Liu
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Yang Luo
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Hao Liu
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Tiejun Zhang
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
Meiyu Hu
Core Lab of Zhongshan Hospital, Fudan University, Shanghai, China
Daqiao Guo
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Xin Xu
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Bin Chen
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Junhao Jiang
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Jue Yang
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Zhenyu Shi
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Ting Zhu
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Yun Shi
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China
Peng Liu
Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
Weiguo Fu
Department of Vascular Surgery, Zhongshan Hospital, and Institute of Vascular Surgery, Fudan University, Shanghai, China; Corresponding authors at: Department of Vascular Surgery of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Background: Peripheral blood mononuclear cells (PBMNCs) and purified CD34+ cells (PCCs) are increasingly being used at treating no-option critical limb ischaemia (NO-CLI). We aimed to compare the efficacies and uncover the advantages associated with each treatment approach. Methods: A randomised single-blinded non-inferiority trial (Number: NCT 02089828) was performed. NO-CLI patients were 1:1 randomised to the PBMNCs and PCCs groups, and compared in relation to safety and efficacy outcomes. The primary efficacy outcomes included major amputation and total amputation over 12 months. The major amputation-free survival (MAFS) and total amputation-free survival (TAFS) rates were calculated. Findings: Fifty patients (25 per group, 47 with thromboangiitis obliterans and 3 with other angiitis) were enrolled, with a median follow-up period of 24.5 months (interquartile range: 17–34 months). One patient in the PCCs group was lost at 2 months and one major amputation occurred in the PBMNCs group at 3 months post-transplantation. The total amputation rates at 6 months post-transplantation were 28.0% in the PCCs group and 16.0% in the PBMNCs group (p = 0.343), and remained unchanged at 12 months. The groups did not differ regarding the MAFS and TAFS (Breslow-Wilcoxon test: p = 0.3014 and p = 0.3414). The PCCs group had a significantly higher probability of rest pain relief than the PBMNCs group (Breslow-Wilcoxon test: p = 0.0454). Interpretation: PCCs was not inferior to PBMNCs at limb salvage in the treatment of angiitis-induced NO-CLI and appeared to induce earlier ischaemia relief. Each cell type had specific advantages. These outcomes require verification from longer-term trials involving larger numbers of patients. Fund: Training program for outstanding academic leaders of Shanghai health and family planning system (Hundred Talent Program，Grant No. 2018BR40); China National Natural Science Funds (Grant No. 30801122); The excellent core member training programme at Zhongshan Hospital, Fudan University, China (Grant No. 2015ZSYXGG02); and Zhongshan Funds for the Institute of Vascular Surgery, Fudan University, China. Clinical trial registration: This study is registered with ClinicalTrials.gov (NCT 02089828). Keywords: Critical limb ischaemia, Cell therapy, Purified CD34+ cells, Peripheral blood mononuclear cells, Limb salvage
