Liang Tiffany W, Jester Andrea, Motaganahalli Raghu L, Wilson Michael G, G'Sell Patricia, Akingba George A, Fajardo Andres, Murphy Michael P
Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind.
Division of Vascular Surgery, Indiana University School of Medicine, Indianapolis, Ind.
J Vasc Surg. 2016 Jun;63(6):1541-5. doi: 10.1016/j.jvs.2016.01.022. Epub 2016 Mar 23.
We have previously shown that autologous bone marrow mononuclear cell (ABMNC) therapy improves measures of limb perfusion, rest pain, wound healing, and amputation-free survival (AFS) at 1 year in patients with critical limb ischemia (CLI). Long-term durability of ABMNC therapy for CLI remains unknown. The objective of the current study was to evaluate long-term clinical outcomes 5 years after treatment.
Data were retrospectively gathered from a database and via a patient survey and review of medical records of patients previously enrolled in this phase I/II trial. AFS, freedom from major amputation, and freedom from major adverse limb events (MALE) were calculated using the product-limit estimate. The incidence of cardiac, malignant, and other medical events relevant to the safety of cell therapy were tabulated during the time from treatment to follow-up.
Twenty-one of the 24 patients (88%) who completed the initial 1-year phase I/II trial were available for the 5-year analysis; AFS was 74% (95% confidence interval [CI], 0.53-0.87), freedom from major amputation was 78% (95% CI, 0.58-0.90), and freedom from MALE was 65% (95% CI, 0.45-0.80). Three patients (14%) had major cardiac events. There were no incidences of malignancies or diagnoses of clinically significant proliferative retinopathy. Fifteen patients (71%) report continued improvement in pain-free walking. Nineteen (90%) patients believed that the study was of significant medical value and would participate again.
ABMNC therapy provides long-term freedom from AFS, major amputation, and MALE that are comparable with other reports of patients who underwent surgical and endovascular interventions for CLI. Furthermore, no patients developed tumorigenesis or clinically significant retinopathy. Because of the limited number of patients studied, our findings will need to be followed up in a larger phase III trial.
我们之前已经表明，自体骨髓单个核细胞（ABMNC）疗法可改善严重肢体缺血（CLI）患者1年时的肢体灌注、静息痛、伤口愈合及无截肢生存率（AFS）。ABMNC疗法对CLI的长期疗效仍不明确。本研究的目的是评估治疗5年后的长期临床结局。
数据通过回顾数据库、患者调查以及查阅先前参与该I/II期试验患者的病历进行回顾性收集。使用乘积限估计法计算AFS、免于大截肢以及免于严重肢体不良事件（MALE）的情况。在从治疗至随访期间，将与细胞治疗安全性相关的心脏、恶性肿瘤及其他医疗事件的发生率制成表格。
完成初始1年期I/II期试验的24例患者中有21例（88%）可进行5年分析；AFS为74%（95%置信区间[CI]，0.53 - 0.87），免于大截肢为78%（95%CI，0.58 - 0.90），免于MALE为65%（95%CI，0.45 - 0.80）。3例患者（14%）发生了严重心脏事件。未发生恶性肿瘤事件或临床显著的增殖性视网膜病变诊断。15例患者（71%）报告无痛行走持续改善。19例（90%）患者认为该研究具有显著医学价值并愿意再次参与。
ABMNC疗法可长期实现AFS、免于大截肢以及免于MALE，与其他接受CLI手术和血管内介入治疗患者的报告结果相当。此外，无患者发生肿瘤形成或临床显著的视网膜病变。由于研究患者数量有限，我们的研究结果需要在更大规模的III期试验中进行随访。
