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51例儿童及青少年白血病幸存者的踝关节骨坏死:经皮间充质干细胞治疗的前瞻性随机研究

Ankle osteonecrosis in fifty-one children and adolescent's leukemia survivors: a prospective randomized study on percutaneous mesenchymal stem cells treatment.

作者信息

Hernigou Philippe, Auregan Jean Charles, Dubory Arnaud, Flouzat Lachaniette Charles Henri, Rouard Hélène

机构信息

Orthopedic Department, Henri Mondor Hospital, University Paris East, Paris, France.

Orthopedic Department, Antoine Beclère Hospital, University Paris West, Paris, France.

出版信息

Int Orthop. 2021 Sep;45(9):2383-2393. doi: 10.1007/s00264-021-05051-z. Epub 2021 Apr 23.

DOI:10.1007/s00264-021-05051-z
PMID:33893522
Abstract

PURPOSE

Corticoid treatment associated with haematologic treatments can lead to ankle osteonecrosis in children's survivors of acute leukemia (ALL). Based on the efficiency of mesenchymal stem cells (MSCs) in hip osteonecrosis, we performed an evaluation of this treatment in 51 children and adolescents who had symptomatic ankle osteonecrosis after therapy for haematologic cancer.

MATERIAL AND METHODS

The 51 patients had a total of 79 osteonecrosis sites on MRI, with 29 talus sites, 18 metaphyseal tibia sites, 12 epiphyseal tibia sites, eight calcaneus sites, six fibula sites, four navicular sites, and two cuboid sites. In this prospective randomized trial, 37 ankles were addressed for cell therapy, 37 others for core decompression alone, and 20 were considered as a control group without treatment. We analyzed the outcome of this treatment osteonecrosis, the number and characteristics of bone marrow mesenchymal cells (MSCs) that could be transplanted, and the risks of tumorigenesis in these patients with haematologic cancers. The patients were operated on over a period of ten years from 2000 to 2010 and were monitored through December 31, 2019.

RESULTS

Despite a normal systemic blood cells count, MSCs in the iliac crest (counted as CFU-F) were in low number (1021 MSCs/mL; range 314-3015) and were of host origin after even allogeneic bone marrow transplantation. Better clinical outcomes (pain, foot and ankle deformity) and osteonecrosis repair on MRI with absence of collapse were obtained in ankles that received cell therapy as compared with those with core decompression alone or those without initial surgery. No tumour was found on MRI at the sites of injection and this study found no increased risk of recurrence or of new cancer in this population after an average follow-up of 15 years.

CONCLUSIONS

These results suggest that autologous MSCs can improve the quality of life of leukemia survivors with ankle osteonecrosis.

摘要

目的

与血液学治疗相关的皮质类固醇治疗可导致急性淋巴细胞白血病(ALL)儿童幸存者出现踝关节骨坏死。基于间充质干细胞(MSC)对髋部骨坏死的治疗效果,我们对51例血液系统癌症治疗后出现有症状踝关节骨坏死的儿童和青少年进行了该治疗的评估。

材料与方法

51例患者的MRI检查共发现79处骨坏死部位,其中距骨部位29处,胫骨干骺端部位18处,胫骨骨骺部位12处,跟骨部位8处,腓骨部位6处,舟骨部位4处,骰骨部位2处。在这项前瞻性随机试验中,37个踝关节接受了细胞治疗,另外37个仅接受了髓芯减压,20个被视为未治疗的对照组。我们分析了这种治疗骨坏死的结果、可移植的骨髓间充质细胞(MSC)的数量和特征,以及这些血液系统癌症患者的肿瘤发生风险。患者在2000年至2010年的十年间接受手术,并一直监测到2019年12月31日。

结果

尽管全身血细胞计数正常,但即使在异基因骨髓移植后,髂嵴中的MSC数量(以CFU-F计数)仍较低(1021个MSC/mL;范围为314 - 3015),且为宿主来源。与仅接受髓芯减压或未接受初始手术的踝关节相比,接受细胞治疗的踝关节在MRI上获得了更好的临床结果(疼痛、足踝畸形)和骨坏死修复,且无塌陷。在注射部位的MRI上未发现肿瘤,并且该研究发现在平均随访15年后,该人群中复发或新发癌症的风险没有增加。

结论

这些结果表明,自体MSC可改善踝关节骨坏死白血病幸存者的生活质量。

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