Long-Term Outcomes of Peripheral Blood Mononuclear Cells in the Treatment of Angiitis-Induced No-Option Critical Limb-Threatening Ischemia

Background: Peripheral blood mononuclear cells (PBMNCs) showed encouraging short outcomes in the treatment of angiitis-induced no-option critical limb-threatening ischemia (AICLTI) in pilot study. We aimed to demonstrate the long-term outcomes of this treatment. Methods: From May 2014 to December 2018, patients diagnosed with AICLTI and treated by autotransplantation of PBMNCs in our center were enrolled and analyzed. The primary endpoint was major amputation-free survival (MAFS), the secondary endpoints included peak pain-free walking time (PPFWT), Wong-Baker FACES pain rating scale score (WFPRSS), labour recovery, ankle-brachial index (ABI), transcutaneous partial oxygen pressure (TcpO2), and SF-36v2 scores. Findings: A total of 58 patients were enrolled. During a minimal follow-up of 36 months, the MAFS was 93.1%, labour competence restored rate was 62.1%. The WFPRSS was decreased from 8.7 ± 1.6 to 1.6 ± 3.2, and PPFWT was significantly improved from 2.9 ± 4.2 minutes to 16.6 ± 6.9 minutes. The quality of life was also significantly improved at each follow-up point. Perfusion evaluating parameters, including ABI and TcPO2 were also significantly improved. No critical adverse event was observed during the treatment and follow-up period. Interpretation: The treatment of AICLTI by autotransplantation of PBMNCs demonstrated encouraging long-term results. It could not only restore the labour competence, improve the quality of life, but also significantly reduced the major amputation rate.  Funding: National Nature Science Funds (81970407), the Training Program for Outstanding Academic Leaders of the Shanghai Health and Family Planning System (2018BR40); the Project of Outstanding Academic Leaders of Shanghai Science and Technology Commission (19XD1401200). Declaration of Interest: All of the authors declare no conflicts of interest. Ethical Approval: This study was approved by the Ethics Committee of the Zhongshan Hospital, Fudan University.