现成的骨髓间充质干细胞对小儿类固醇难治性急性移植物抗宿主病的疗效。

Blood cell therapy Pub Date : 2023-12-15 eCollection Date: 2024-02-25 DOI:10.31547/bct-2023-020
Hirohito Kubota, Yuki Arakawa, Yoshitaka Mizushima, Tomoya Irikura, Mai Watakabe, Takahiro Ishikawa, Ryota Kaneko, Mamoru Honda, Yuichi Mitani, Kohei Fukuoka, Makiko Mori, Koichi Oshima, Katsuyoshi Koh
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引用次数: 0

摘要

简介Temcell是一种间充质干细胞(MSC)产品,在日本被批准用于治疗类固醇难治性急性移植物抗宿主病(SR-aGVHD)。然而,有关Temcell对儿科患者疗效的报道很少,间充质干细胞疗法是否适合用于儿科SR-aGVHD也仍有待确定:我们对一组异基因造血移植后使用Temcell治疗SR-aGVHD的儿科患者进行了回顾性评估。根据制造商的说明,间充质干细胞的静脉输注剂量为 2 × 106 个细胞/千克:12名患者接受了18个周期的间充质干细胞治疗(中位年龄为10.3 [1.7-17.8]岁),其中4人接受了额外的治疗周期(一个周期:n = 3,三个周期:n = 1)。在接受间充质干细胞治疗前,3名患者的副坏死严重程度为I-II级,9名患者为III-IV级(肠道3-4期,n=7;肝脏3-4期,n=2)。间充质干细胞治疗前接受免疫抑制治疗的中位数为2次(范围:1-5次)。第一个间充质干细胞周期的总体反应率最高,达到83%,其中6名患者获得完全反应(CR),8周后泼尼松的平均日剂量减少了49%。首次应答的中位时间为 3.5 天(范围:2-15 天)。四名因复发或持续GVHD而再次使用间充质干细胞的患者中,有两人达到了CR。三年总生存率为 69.4%,三年无失败生存率为 22.2%,中位无失败生存期为 4.9 个月。间充质干细胞疗法无明显副作用:结论:间充质干细胞疗法似乎是治疗小儿SR-aGVHD的一种有效而安全的方法,具有节省类固醇的作用,且再次给药后疗效令人满意。还需要进一步的研究来确定它与其他治疗方法的适当结合以及再次给药间充质干细胞的最佳使用方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease.

Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease.

Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease.

Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease.

Introduction: Temcell is a mesenchymal stem cell (MSC) product approved for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in Japan. However, reports regarding Temcell's efficacy in pediatric patients have been scarce, and the appropriate use of MSC therapy against pediatric SR-aGVHD also remains to be determined.

Patients and methods: We retrospectively assessed a cohort of pediatric patients treated with Temcell for SR-aGVHD following allogeneic hematopoietic transplantation. MSCs were infused intravenously at a dose of 2 × 106 cells/kg according to the manufacturer's instructions.

Results: Twelve patients received eighteen cycles of MSC therapy (median age, 10.3 [1.7-17.8] years), with four receiving additional cycles (one cycle: n = 3, three cycles: n = 1). The severity of aGVHD before MSC therapy was grade I-II in three patients and grade III-IV in nine patients (gut stage 3-4, n= 7; liver stage 3-4; n =2). The median number of immunosuppressive therapy regimens received prior to MSC administration was two (range: 1-5). The first MSC cycle displayed the best overall response rate of 83%, including six patients with a complete response (CR) and with a 49% reduction in the mean daily dose of prednisone after eight weeks. The median time to first response was 3.5 days (range: 2-15 days). Two of the four patients who were re-administered MSCs for recurrent or persistent GVHD achieved a CR. The three-year overall survival rate was 69.4%, while the three-year failure free survival (FFS) rate was 22.2%, with a median FFS of 4.9 months. There were no observable side effects of MSC therapy.

Conclusions: MSC therapy appears to be an effective and safe treatment for pediatric SR-aGVHD, with a steroid-sparing effect and satisfactory efficacy upon re-administration. Further studies are needed to determine its appropriate combination with additional treatments and the optimal use of re-administration of MSCs.

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