Philippe Hernigou1, Yasuhiro Homma2, Charles-Henri Flouzat-Lachaniette1, Alexandre Poignard1, Nathalie Chevallier1, Helene Rouard1. 1. Department of Orthopaedic Surgery (P.H., C.-H.F.-L., and A.P.) and EFS Cell Therapy Facility (N.C. and H.R.), University Paris East, Hospital Henri Mondor, 51 avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France. E-mail address for P. Hernigou: philippe.hernigou@wanadoo.fr. 2. Juntendo University, Hongo 2-1-1, Bunko-Ku, Tokyo 113-8421, Japan.
Abstract
BACKGROUND: There is concern that regenerative cell-based therapies could result in increased risk of tumor formation. We investigated the long-term risks for systemic and site-specific cancers in patients who had received autologous bone marrow-derived stromal progenitor cells to treat orthopaedic lesions. METHODS: A total of 1873 patients were treated from 1990 to 2006 with bone marrow-derived concentrated cells. Patients were monitored for cancer incidence from the date of the first operation (1990) until death, or until December 31, 2011. The mean follow-up time was 12.5 years (range, five to twenty-two years). The average number of colony-forming unit fibroblasts returned to the patients was 483,000 fibroblasts (range, 62,000 to 2,095,000 fibroblasts). The primary outcome was to evaluate with radiographs and/or magnetic resonance imaging the risk of tumorigenesis at the cell therapy treatment sites. The secondary outcome was to evaluate the risk of cancer diagnosed in areas other than the treatment site during the follow-up period. The relative risk of cancer was expressed as the ratio of observed and expected number of cases, that is, the standardized incidence ratio, according to the cancer incidence in the French population. RESULTS: No tumor formation was found at the treatment sites on the 7306 magnetic resonance images and 52,430 radiographs among the 1873 patients. Fifty-three cancers were diagnosed in areas other than the treatment site. On the basis of cancer incidence in the general population during the same period, the expected number of cancers was between ninety-seven and 108 for the same age and sex distribution. The range of the standardized incidence ratio for the follow-up period was between 0.49 and 0.54 (95% confidence interval, 0.30 to 0.80). CONCLUSIONS: This study found no increased cancer risk in patients after application of autologous cell-based therapy using bone marrow-derived stromal progenitor cells either at the treatment site or elsewhere in the patients after an average follow-up period of 12.5 years.
BACKGROUND: There is concern that regenerative cell-based therapies could result in increased risk of tumor formation. We investigated the long-term risks for systemic and site-specific cancers in patients who had received autologous bone marrow-derived stromal progenitor cells to treat orthopaedic lesions. METHODS: A total of 1873 patients were treated from 1990 to 2006 with bone marrow-derived concentrated cells. Patients were monitored for cancer incidence from the date of the first operation (1990) until death, or until December 31, 2011. The mean follow-up time was 12.5 years (range, five to twenty-two years). The average number of colony-forming unit fibroblasts returned to the patients was 483,000 fibroblasts (range, 62,000 to 2,095,000 fibroblasts). The primary outcome was to evaluate with radiographs and/or magnetic resonance imaging the risk of tumorigenesis at the cell therapy treatment sites. The secondary outcome was to evaluate the risk of cancer diagnosed in areas other than the treatment site during the follow-up period. The relative risk of cancer was expressed as the ratio of observed and expected number of cases, that is, the standardized incidence ratio, according to the cancer incidence in the French population. RESULTS: No tumor formation was found at the treatment sites on the 7306 magnetic resonance images and 52,430 radiographs among the 1873 patients. Fifty-three cancers were diagnosed in areas other than the treatment site. On the basis of cancer incidence in the general population during the same period, the expected number of cancers was between ninety-seven and 108 for the same age and sex distribution. The range of the standardized incidence ratio for the follow-up period was between 0.49 and 0.54 (95% confidence interval, 0.30 to 0.80). CONCLUSIONS: This study found no increased cancer risk in patients after application of autologous cell-based therapy using bone marrow-derived stromal progenitor cells either at the treatment site or elsewhere in the patients after an average follow-up period of 12.5 years.
Authors: Philippe Hernigou; Charles Henri Flouzat Lachaniette; Jerome Delambre; Nathalie Chevallier; Helene Rouard Journal: Int Orthop Date: 2014-06-07 Impact factor: 3.075
Authors: Jacques Hernigou; Laure Picard; Alexandra Alves; Jonathan Silvera; Yasuhiro Homma; Philippe Hernigou Journal: Int Orthop Date: 2014-05-03 Impact factor: 3.075
Authors: Louis-Romée Le Nail; Julien Stanovici; Joseph Fournier; Marie Splingard; Jorge Domenech; Philippe Rosset Journal: Int Orthop Date: 2014-04-13 Impact factor: 3.075
Authors: Christopher J Centeno; Hasan Al-Sayegh; Michael D Freeman; Jay Smith; William D Murrell; Rostyslav Bubnov Journal: Int Orthop Date: 2016-03-30 Impact factor: 3.075