title: Adverse events during treatment of critical limb ischemia with autologous peripheral blood mononuclear cell implant.
abstract: OBJECTIVE
  Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work.
  
  
  METHODS
  We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks.
  
  
  RESULTS
  Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.
  
  
  CONCLUSIONS
  Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.
authors.affiliation: Department of Surgery, University Hospital, Örebro, Sweden. thomas.jonsson@surgsci.uu.se
authors.forename: T B
authors.initials: TB
authors.lastname: Jonsson
authors.forename: T
authors.initials: T
authors.lastname: Larzon
authors.forename: B
authors.initials: B
authors.lastname: Arfvidsson
authors.forename: U
authors.initials: U
authors.lastname: Tidefelt
authors.forename: C G
authors.initials: CG
authors.lastname: Axelsson
authors.forename: M
authors.initials: M
authors.lastname: Jurstrand
authors.forename: L
authors.initials: L
authors.lastname: Norgren
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D015901:Angiography, Digital Subtraction; D055109:Ankle Brachial Index; D016638:Critical Illness; D016207:Cytokines / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006333:Heart Failure / Q000209:etiology / Q000401:mortality; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007511:Ischemia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D023821:Limb Salvage; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000209:etiology / Q000401:mortality; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D010147:Pain Measurement; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000008:administration & dosage; D012086:Reoperation; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden; D013927:Thrombosis / Q000209:etiology / Q000401:mortality; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014945:Wound Healing
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim