Phase III clinical trial of autologous CD34 + cell transplantation to accelerate fracture nonunion repair

BMC Medicine

Research Article

Keisuke Oe¹  Tomoyuki Matsumoto¹  Yutaka Mifune¹  Tomoaki Fukui¹  Ryosuke Kuroda¹  Takahiro Niikura¹  Shinichiro Kawamoto²  Hiroshi Matsuoka³  Yoshiharu Miyata³  Kimikazu Yakushijin³  Hironobu Minami³  Atsuhiko Kawamoto⁴  Yasuyuki Fujita⁴  Tatsuo Kagimura⁴ 

[1] Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-Ku, 650-0017, Kobe, Japan;Department of Transfusion Medicine and Cell Therapy, Kobe University Hospital, Chuo-Ku, 650-0017, Kobe, Japan;Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Chuo-Ku, 650-0017, Kobe, Japan;Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Chuo-Ku, 650-0047, Kobe, Japan;

关键词: Clinical trial;    Phase III;    CD34 + cell;    Transplantation;    Fracture nonunion;   

DOI  :  10.1186/s12916-023-03088-y

 received in 2023-06-18, accepted in 2023-09-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundWe previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients.MethodsCD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded.ResultsAll fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16–6.85); moreover, no safety concerns were observed.ConclusionsOur findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion.Trial registrationUMIN-CTR, UMIN000022814. Registered on 22 June 2016.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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