218. Randomized Prospective Clinical Trial to Evaluate Efficacy and Safety in Lumbar Fusion Surgery of Implantation of Autologous Bone Marrow Mesenchymal Cells Expanded Ex Vivo and Combined with Allogeneic Bone Tissue, Compared with Autologous Iliac Crest Graft: Part I: Radiological Findings

BACKGROUND CONTEXT Spinal fusion is a widely used surgical technique for a great variety of spine pathologies. Spinal fusion using the patient's iliac crest is the standard surgical technique, although it is associated with a relevant percentage of failures and local morbidity of the bone donor area. PURPOSE The main objective of this clinical trial was to evaluate the feasibility, safety, and efficacy of implantation of a scaffold of heterologous human cancellous bone tissue seeded with autologous bone marrow mesenchymal cells expanded ex vivo (XCEL-MT-OSTEO-ALPHA) and to compare the resulting intervertebral fusion as evaluated by radiography and computed tomography (CT) with that obtained in patients who received autologous iliac crest graft. STUDY DESIGN/SETTING Multicenter, prospective, open-label, randomized, parallel and single-dose phase I-II study (EudraCT No.2010-023999-12; NCT01552707). PATIENT SAMPLE Sixty-five patients from 5 centers (mean age, 61.05 years; 65.6% female) with degenerative spondylolisthesis (79.4%) and/or disc disease at L4-L5. OUTCOME MEASURES Adverse events were recorded and fusion was assessed by radiography (3, 6, and 12 months) and CT (6 and 12 months). Bone fusion status was evaluated according to previously established qualitative criteria by a radiologist who was blind to treatment allocation. METHODS Patients underwent instrumented circumferential fusion at L4-L5; transforaminal lumbar interbody fusion (TLIF) was performed using an intersomatic cage filled with autologous iliac crest graft, and intertransverse fusion consisted of local bone graft on the TLIF side and randomly assigned XCEL-MT-OSTEO-ALPHA (Group A, treatment) or autologous iliac crest graft (Group B, control) on the contralateral side.Patients underwent follow-up for 1 year. RESULTS Groups A and B comprised 31 and 34 patients, respectively. There were no significant differences in preoperative variables between groups, and no serious adverse reactions were associated with the product. Compared with controls the treatment group showed a significantly higher rate of intertransverse fusion as determined by radiography at 3 (85.7% vs 56.3%), 6 (81.5% vs 48.3%), and 12 months (96.3% vs 51.7%) and by CT at 6 months (96.3% vs 54.8%). One year after surgery the intertransverse fusion rate was higher in the treatment than the control group (86.2% vs 66.7%), although this difference was not significant. CONCLUSIONS XCEL-MT-OSTEO-ALPHA is a viable and safe product for use in lumbar fusion surgery. Radiological fusion rates in the area in which the product was applied were significantly higher than those obtained with autologous iliac crest graft. FDA DEVICE/DRUG STATUS XCEL-MT-OSTEO-ALPHA (Not approved for this indication) Spinal fusion is a widely used surgical technique for a great variety of spine pathologies. Spinal fusion using the patient's iliac crest is the standard surgical technique, although it is associated with a relevant percentage of failures and local morbidity of the bone donor area. The main objective of this clinical trial was to evaluate the feasibility, safety, and efficacy of implantation of a scaffold of heterologous human cancellous bone tissue seeded with autologous bone marrow mesenchymal cells expanded ex vivo (XCEL-MT-OSTEO-ALPHA) and to compare the resulting intervertebral fusion as evaluated by radiography and computed tomography (CT) with that obtained in patients who received autologous iliac crest graft. Multicenter, prospective, open-label, randomized, parallel and single-dose phase I-II study (EudraCT No.2010-023999-12; NCT01552707). Sixty-five patients from 5 centers (mean age, 61.05 years; 65.6% female) with degenerative spondylolisthesis (79.4%) and/or disc disease at L4-L5. Adverse events were recorded and fusion was assessed by radiography (3, 6, and 12 months) and CT (6 and 12 months). Bone fusion status was evaluated according to previously established qualitative criteria by a radiologist who was blind to treatment allocation. Patients underwent instrumented circumferential fusion at L4-L5; transforaminal lumbar interbody fusion (TLIF) was performed using an intersomatic cage filled with autologous iliac crest graft, and intertransverse fusion consisted of local bone graft on the TLIF side and randomly assigned XCEL-MT-OSTEO-ALPHA (Group A, treatment) or autologous iliac crest graft (Group B, control) on the contralateral side.Patients underwent follow-up for 1 year. Groups A and B comprised 31 and 34 patients, respectively. There were no significant differences in preoperative variables between groups, and no serious adverse reactions were associated with the product. Compared with controls the treatment group showed a significantly higher rate of intertransverse fusion as determined by radiography at 3 (85.7% vs 56.3%), 6 (81.5% vs 48.3%), and 12 months (96.3% vs 51.7%) and by CT at 6 months (96.3% vs 54.8%). One year after surgery the intertransverse fusion rate was higher in the treatment than the control group (86.2% vs 66.7%), although this difference was not significant. XCEL-MT-OSTEO-ALPHA is a viable and safe product for use in lumbar fusion surgery. Radiological fusion rates in the area in which the product was applied were significantly higher than those obtained with autologous iliac crest graft.