title: A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia.
abstract: BACKGROUND
  Critical limb ischemia portends a risk of major amputation of 25% to 35% within 1 year of diagnosis. Preclinical studies provide evidence that intramuscular injection of autologous CD34+ cells improves limb perfusion and reduces amputation risk. In this randomized, double-blind, placebo-controlled pilot study, we evaluated the safety and efficacy of intramuscular injections of autologous CD34+ cells in subjects with moderate or high-risk critical limb ischemia, who were poor or noncandidates for surgical or percutaneous revascularization (ACT34-CLI).
  
  
  RESULTS
  Twenty-eight critical limb ischemia subjects were randomized and treated: 7 to 1 × 10(5) (low-dose) and 9 to 1 × 10(6) (high-dose) autologous CD34+ cells/kg; and 12 to placebo (control). Intramuscular injections were distributed into 8 sites within the ischemic lower extremity. At 6 months postinjection, 67% of control subjects experienced a major or minor amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.137). This trend continued at 12 months, with 75% of control subjects experiencing any amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.058). Amputation incidence was lower in the combined cell-treated groups compared with control group (6 months: P=0.125; 12 months: P=0.054), with the low-dose and high-dose groups individually showing trends toward improved amputation-free survival at 6 months and 12 months. No adverse safety signal was associated with cell administration.
  
  
  CONCLUSIONS
  This study provides evidence that intramuscular administration of autologous CD34+ cells was safe in this patient population. Favorable trends toward reduced amputation rates in cell-treated versus control subjects were observed. These findings warrant further exploration in later-phase clinical trials.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00616980.
authors.affiliation: Division of Cardiovascular Medicine, Northwestern Memorial Hospital, Chicago, IL, USA. douglas_losordo@baxter.com
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
authors.forename: Farrell
authors.initials: F
authors.lastname: Mendelsohn
authors.forename: William
authors.initials: W
authors.lastname: Marston
authors.forename: Vickie R
authors.initials: VR
authors.lastname: Driver
authors.forename: Melhem
authors.initials: M
authors.lastname: Sharafuddin
authors.forename: Victoria
authors.initials: V
authors.lastname: Teodorescu
authors.forename: Bret N
authors.initials: BN
authors.lastname: Wiechmann
authors.forename: Charles
authors.initials: C
authors.lastname: Thompson
authors.forename: Larry
authors.initials: L
authors.lastname: Kraiss
authors.forename: Teresa
authors.initials: T
authors.lastname: Carman
authors.forename: Suhail
authors.initials: S
authors.lastname: Dohad
authors.forename: Paul
authors.initials: P
authors.lastname: Huang
authors.forename: Candice E
authors.initials: CE
authors.lastname: Junge
authors.forename: Kenneth
authors.initials: K
authors.lastname: Story
authors.forename: Tara
authors.initials: T
authors.lastname: Weistroffer
authors.forename: Tina M
authors.initials: TM
authors.lastname: Thorne
authors.forename: Meredith
authors.initials: M
authors.lastname: Millay
authors.forename: John Paul
authors.initials: JP
authors.lastname: Runyon
authors.forename: Robert
authors.initials: R
authors.lastname: Schainfeld
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D000704:Analysis of Variance; D018952:Antigens, CD34 / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D016638:Critical Illness; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000503:physiopathology / Q000601:surgery*; D023821:Limb Salvage; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011788:Quality of Life; D020127:Recovery of Function; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013234:Stem Cells / Q000276:immunology*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014481:United States; D014945:Wound Healing
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers