title: Autologous bone marrow mononuclear cell therapy for critical limb ischemia is effective and durable.
abstract: 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.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Tiffany W
authors.initials: TW
authors.lastname: Liang
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jester
authors.affiliation: Division of Vascular Surgery, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Raghu L
authors.initials: RL
authors.lastname: Motaganahalli
authors.affiliation: Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wilson
authors.affiliation: Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Patricia
authors.initials: P
authors.lastname: G'Sell
authors.affiliation: Division of Vascular Surgery, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: George A
authors.initials: GA
authors.lastname: Akingba
authors.affiliation: Division of Vascular Surgery, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Andres
authors.initials: A
authors.lastname: Fajardo
authors.affiliation: Division of Vascular Surgery, Indiana University School of Medicine, Indianapolis, Ind. Electronic address: mipmurph@iupui.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016638:Critical Illness; D016208:Databases, Factual; D018572:Disease-Free Survival; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D053208:Kaplan-Meier Estimate; D023821:Limb Salvage; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D017060:Patient Satisfaction; D020127:Recovery of Function; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D016138:Walking; D055815:Young Adult