Thurs., 10/18/07 Reconstruction, Paper #17, 4:57 pm OTA-2007
High-Dose Stem and Progenitor Cell Therapy for Refractory Long-Bone Nonunions: Final Results of a Multicenter Phase I/II Clinical Study
Matthew L. Jimenez, MD1 (a-Aastrom); Thomas R. Lyon, MD2 (a,b-Aastrom);
Gregory Nowinski, MD3 (a-Aastrom); Jeffrey Balazsy, MD3 (a-Aastrom);
James A. Goulet, MD4 (a-Aastrom); Janet Hock, PhD5 (e-Aastrom); Tracy A. Sferra, MS1 (n);
1Illinois Bone and Joint Institute, Chicago, Illinois, USA;
2Lutheran Medical Center, Brooklyn, New York, USA;
3William Beaumont Hospital, Royal Oak, Michigan, USA;
4University of Michigan Medical Center, Ann Arbor, Michigan, USA;
5Maine Institute for Human Genetics and Health, Brewer, Maine, USA
Purpose: This multicenter prospective clinical trial explored the use of a novel autologous bone marrow-derived cultured cell mixture expanded ex vivo containing large numbers of stem and progenitor cells (tissue repair cells [TRCs]), for the treatment of long-bone nonunions. This FDA-approved open label multicenter phase I/II clinical trial evaluated a prospective case series of appendicular skeletal nonunions treated with open reduction and internal fixation and grafted with a volume of ex vivo expanded and isolated stem and progenitor cells delivered on a mineralized allograft carrier.
Methods: 36 long-bone nonunion patients, 13 females and 23 males aged 19 to 79 years, with at least one previously failed fracture fixation were enrolled in the study. Nonunions were débrided, decorticated, and stabilized as required with standard fixation techniques. Autologous TRCs were obtained from a small-volume aspirate of each patient’s iliac crest, and then volume expanded and processed for 12 to 14 days by a single-pass perfusion in a closed and automated system. The average number of TRCs available per patient for each nonunion surgery was 175 million cells suspended in 150 cc of nutrient solution. A fixed dose of 3 million cells per 1 cc of mineralized allograft was applied to each nonunion site.
Results: 36 patients were enrolled and treated; data is actively being collected and analyzed. To date, bone bridging was observed with plain radiographs or computed tomography in 18 of 20 patients (90%) at 12 months and 26 of 31 patients (84%) at 6 months. Callus formation was observed in 19 of 20 patients (95%) at 12 months and 30 of 31 patients (97%) at 6 months. There were no cell-related adverse events reported.
Conclusions and Significance: These multicenter clinical data demonstrate bone repair using large numbers of autologous stem and progenitor cells. Our early results show that TRCs are safe and efficacious for recalcitrant long-bone nonunions and may represent a new viable option for patient treatment.
If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.
• The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an “off label” use). ◆FDA information not available at time of printing.