Abstract 519: Therapeutic Angiogenesis by Peripheral Blood Mononuclear Cells and its Rationale for Designing a New Trial

Abstract

Background: Clinical trials of therapeutic angiogenesis that treat chronic critical limb ischemia (CLI) are revealing mixed results. This may partly be due to unapt patient selection or suboptimal study protocols. Here, from our registry, we report demographic and procedural characteristics of patients who underwent major limb amputation despite therapeutic angiogenesis. Methods: Registry of CLI patients who were treated by peripheral blood mononuclear cell (PBMNC) implantation was retrospectively analyzed. Cases that underwent major limb amputation within 6 months of the therapy were further investigated to clarify any features that might have affected their limb outcomes. Results and Discussions: Among total of 112 patients in the registry, eight cases lost to follow up and were excluded from this study. Sixteen patients (16/104, 15.4%) underwent major limb amputation within 6 months after therapeutic angiogenesis. Six amputees had active infection in the treated limb. Unlike excellent outcome by bone marrow derived cells, any patients with systemic sclerosis treated by PBMNC had poor limb salvage. However, half (8/16) of the amputees had experienced blood flow recovery, at least for transient period of two weeks. Among these patients, five limbs showed significant recovery of crural blood flow, while in the ipsilateral foot, distal blood flow deteriorated, indicating the flow steal phenomenon induced by cell therapy, which induces strong vasodilatation. Excluding patients with active infection or systemic sclerosis halved the limb amputation rate. Careful selection of sites to implant cells according to anatomical distribution of arterial blood flow could even have improved the limb salvage rate. Conclusion: When designing a clinical trial of therapeutic angiogenesis, (1) excluding patients with active infections, (2) proper treatment site considering anatomical distribution of arterial blood flow to avoid steal phenomenon, and (3) selection of cell source according to etiology of CLI, may clarify the efficacy of therapeutic angiogenesis.