Bone Marrow Autograft in Limb Ischemia (BALI)

BALI (Bone marrow Autograft in Limb Ischemia) is a randomized double-blind trial comparing implantation of bone marrow - mononuclear cells versus placebo in patients presenting with critical leg ischemia and no surgical option. The main end point is the survival without major amputation 6 months after implantation. Biological studies are performed on bone marrow mononuclear cells (BM-MNC) to evaluate their angiogenic properties.

One hundred and ten patients with critical leg ischemia and no surgical option will be included. A bone marrow harvest (500 mL under general anaesthesia) is performed and BM-MNC are separated and concentrated (30 mL) for all included patients. For half of them, the BM-MNC are implanted on the same day whereas the others are implanted with a placebo cell-product (30 mL saline with 4 ml peripheral blood). For these patients the BM-MNC are cryo-conserved. Only the cell therapy unit, neither the patient, nor the clinician, know whether BM-MNC or placebo is implanted. The main end point is the survival without major amputation 6 months after implantation. After this delay it is possible to use previously cryo-conserved BM-MNC. Likewise biological studies are performed on BM-MNC: flow-cytometry analysis of progenitor cells content, proteins and mRNAs expression, induced angiogenesis in animal models.

A bone marrow harvest (500 mL under general anaesthesia) is performed and BM-MNC are separated and concentrated (30mL). A placebo cell-product (30 mL saline with 4 ml peripheral blood) is implanted and the BM-MNC are cryo-conserved. Only the cell therapy unit, neither the patient, nor the clinician, know whether BM-MNC or placebo is implanted. After 6 months, it is possible to use previously cryo-conserved BM-MNC.

A bone marrow harvest (500 mL under general anaesthesia) is performed and BM-MNC are separated and concentrated (30mL) . The BM-MNC are implanted on the same day. Only the cell therapy unit, neither the patient, nor the clinician, know whether BM-MNC or placebo is implanted

Inclusion Criteria: Critical limb ischemia No possible surgical treatment Exclusion Criteria: Ongoing infectious disease Gangrene extending beyond the digits Diabetes mellitus with HbA1c > 7.5% or with proliferative retinopathy History of malignant disease Contra-indication to general anaesthesia Chronic haemodialysis Prothrombin Time < 50% Recent onset (within 3 months) of myocardial infarction or brain infarction Contra-indication to modification of anti-platelet or anticoagulant therapy History of heparin-induced thrombocytopenia Unexplained haematological abnormality