接受自体骨髓细胞浓缩物治疗骨科疾病的患者癌症风险并未增加。

Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate.

机构信息

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:

Juntendo University, Hongo 2-1-1, Bunko-Ku, Tokyo 113-8421, Japan.

出版信息

J Bone Joint Surg Am. 2013 Dec 18;95(24):2215-21. doi: 10.2106/JBJS.M.00261.

DOI:10.2106/JBJS.M.00261

PMID:24352775

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.

摘要

背景

人们担心基于再生细胞的疗法会增加肿瘤形成的风险。我们研究了接受自体骨髓源性基质祖细胞治疗骨科病变的患者的全身和特定部位癌症的长期风险。

方法

1990 年至 2006 年间，共有 1873 名患者接受骨髓源性浓缩细胞治疗。从第一次手术（1990 年）的日期开始，对患者进行癌症发病率监测，直至死亡或 2011 年 12 月 31 日。平均随访时间为 12.5 年（5-22 年）。患者平均回输的成纤维细胞集落形成单位数为 483000 个成纤维细胞（62000-2095000 个成纤维细胞）。主要结局是通过影像学检查评估细胞治疗治疗部位的肿瘤形成风险。次要结局是评估随访期间治疗部位以外区域诊断出的癌症风险。癌症的相对风险表示为观察到的和预期的病例数之比，即标准化发病比，根据法国人口的癌症发病率计算。

结果

在 1873 名患者的 7306 份磁共振成像和 52430 份放射图像中，未发现治疗部位有肿瘤形成。在治疗部位以外的区域诊断出 53 例癌症。根据同期一般人群的癌症发病率，相同年龄和性别分布的预期癌症数在 97 至 108 之间。随访期间标准化发病比的范围为 0.49 至 0.54（95%置信区间，0.30-0.80）。