The efficacy of mesenchymal stem cells in bronchiolitis obliterans syndrome after allogeneic HSCT: A multicenter prospective cohort study
The efficacy of mesenchymal stem cells in bronchiolitis obliterans syndrome after allogeneic HSCT: A multicenter prospective cohort study
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间充质干细胞对同种异体 HSCT 后闭塞性细支气管炎综合征的疗效：一项多中心前瞻性队列研究
DOI：
10.1016/j.ebiom.2019.09.039
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发表时间：
2019-11-01
期刊：
影响因子：
11.1
通讯作者：
Liu, Qifa
中科院分区：
文献类型：
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作者：
Chen, Shan;Zhao, Ke;Liu, Qifa
背景：allo-HSCT后闭塞性细支气管炎综合征（BOS）是一种严重的并发症，治疗选择有限。我们的目的是评估骨髓间充质干细胞（MSCs）在BOS allo-HSCT.Methods后的有效性和安全性：本多中心前瞻性队列研究纳入了81名allo-HSCT受者，其BOS在6个月内被诊断。泼尼松和阿奇霉素联合或不联合MSC的选择基于患者的偏好（MSC n = 49，非MSC n = 32）。主要终点是3个月时的缓解率，定义为实现FEV 1改善或类固醇节省的患者比例。该试验已在ClinicalTrials.gov上注册（NCT 02543073）。结果：MSC组和非MSC组的缓解率分别为35/49例患者（71%，95%CI 59至84%）和14/32例患者（44%，27至61%）（p = 0.013）。与非MSC组相比，添加MSC与FEV 1下降率变化的更好差异相关（53 mL/月，2至103; p = 0.040）。MSC和非MSC组诊断后3年总生存率分别为70.6%（55.9 - 85.3%）和58.2%（36.1 - 78.5%）（p = 0.21）。临床改善伴随着产生白细胞介素（IL）-10的CD 5 +B细胞的显著增加。两组感染率和白血病复发率无统计学差异。骨髓间充质干细胞耐受性良好，无严重不良事件发生。解释：骨髓间充质干细胞为异基因造血干细胞移植后BOS提供了一种有效和安全的治疗选择。我们的研究加强了MSC治疗BOS临床应用的证据。这些数据还提供了新的见解，以潜在的生物机制，间充质干细胞治疗和支持进一步调查，在更大的随机对照试验。资助：国家重点研发计划、国家自然科学基金、广州市健康协同创新重大项目、广东省科技规划项目。(c)2019作者（S）由爱思唯尔公司出版
Background: Bronchiolitis obliterans syndrome (BOS) after allo-HSCT is a devastating complication with limited therapeutic options. We aimed to assess the efficacy and safety of mesenchymal stem cells (MSCs) in BOS after allo-HSCT.Methods: This multicenter prospective cohort study enrolled 81 allo-HSCT recipients whose BOS were diagnosed within 6 months. The choice of prednisone and azithromycin combined with or without MSCs was based on patient preferences (MSC n = 49, non-MSC n = 32). The primary endpoint was response rate at 3 months, defined as the proportion of patients achieving FEV1 improvement or steroid sparing. The trial was registered at ClinicalTrials.gov (NCT02543073).Findings: Response rate was 35/49 patients (71%, 95% CI 59 to 84%) and 14/32 (44%, 27 to 61%) in MSC and non-MSC group, respectively (p = 0.013). The addition of MSCs was associated with a better difference for change in FEV1 rate of decline, compared to non-MSC group (53 mL/months, 2 to 103; p = 0.040). The 3-year overall survival post-diagnosis was 70.6% (55.9 to 85.3%) and 58.2% (36.1 to 78.5%) in MSC and non-MSC group, respectively (p = 0.21). Clinical improvement was accompanied by a significant increase of interleukin (IL)-10-producing CD5+B cells. There was no statistical difference in the rates of infections and leukemia relapse between the two groups. MSCs were well-tolerated with no serious adverse events.Interpretation: MSCs offer an effective and safe therapeutic option for BOS after allo-HSCT. Our study strengthens evidence for clinical use of MSC therapy in BOS. These data also provide novel insight into potential biological mechanisms of MSC treatment and support further investigation in larger randomized controlled trials.Funding: National Key R&D Program of China, National Natural Science Foundation of China, Health Collaborative Innovation Major Projects of Guangzhou City, Science and Technology Planning Project of Guangdong Province. (c) 2019 The Author(s). Published by Elsevier B.V.