Abstract：
OBJECTIVE: Cytopenias after allogeneic stem cell transplantation (allo-SCT) are a common complication, the underlying pathogenic mechanisms of which remain incompletely understood. Multipotent mesenchymal stromal/stem cell (MSC) therapy has been successfully employed in the treatment of immune-related disorders and can aid in the restoration of the hematopoietic niche.
METHODS: A phase II clinical trial to assess the efficacy and safety of administering four sequential doses of ex-vivo expanded bone marrow MSCs from a third-party donor to patients with persistent severe cytopenias after allo-SCT was performed.
RESULTS: The overall response rate on day 90 was 75% among the 27 evaluable patients (comprising 12 complete responses, 8 partial responses, and 7 with no response). The median time to respond was 14.5 days. Responses were observed across different profiles, including single or multiple affected lineages, primary or secondary timing, and potential immune-mediated or post-infectious pathophysiology versus idiopathic origin. With a median follow-up for surviving patients of 85 months after MSC infusion, 53% of patients are alive. Notably, no adverse events related to MSC therapy were reported.
CONCLUSIONS: In summary, the sequential infusion of third-party MSCs emerges as a viable and safe therapeutic option, exhibiting potential benefits for patients experiencing cytopenias following allo-SCT.
METHODS: A phase II clinical trial to assess the efficacy and safety of administering four sequential doses of ex-vivo expanded bone marrow MSCs from a third-party donor to patients with persistent severe cytopenias after allo-SCT was performed.
RESULTS: The overall response rate on day 90 was 75% among the 27 evaluable patients (comprising 12 complete responses, 8 partial responses, and 7 with no response). The median time to respond was 14.5 days. Responses were observed across different profiles, including single or multiple affected lineages, primary or secondary timing, and potential immune-mediated or post-infectious pathophysiology versus idiopathic origin. With a median follow-up for surviving patients of 85 months after MSC infusion, 53% of patients are alive. Notably, no adverse events related to MSC therapy were reported.
CONCLUSIONS: In summary, the sequential infusion of third-party MSCs emerges as a viable and safe therapeutic option, exhibiting potential benefits for patients experiencing cytopenias following allo-SCT.
摘要：
目的：异基因干细胞移植（allo-SCT）后的细胞减少是常见的并发症，其潜在的致病机制仍未完全理解。多能间充质基质/干细胞（MSC）疗法已成功用于治疗免疫相关疾病，并有助于恢复造血生态位。
方法：一项II期临床试验，旨在评估在进行allo-SCT后，对患有持续性严重血细胞减少症的患者给予来自第三方供体的4种连续剂量的离体扩增骨髓间充质干细胞的疗效和安全性。
结果：在27名可评估患者中，第90天的总体缓解率为75％（包括12个完全缓解，8部分反应，和7没有回应)。中位应答时间为14.5天。在不同的配置文件中观察到了反应，包括单个或多个受影响的谱系，主要或次要计时，和潜在的免疫介导或感染后病理生理学与特发性起源。MSC输注后存活患者的中位随访时间为85个月，53%的患者还活着。值得注意的是,未报告与MSC治疗相关的不良事件.
结论：总之，顺序输注第三方MSCs是一种可行且安全的治疗选择，在allo-SCT后出现血细胞减少症的患者表现出潜在的益处。
方法：一项II期临床试验，旨在评估在进行allo-SCT后，对患有持续性严重血细胞减少症的患者给予来自第三方供体的4种连续剂量的离体扩增骨髓间充质干细胞的疗效和安全性。
结果：在27名可评估患者中，第90天的总体缓解率为75％（包括12个完全缓解，8部分反应，和7没有回应)。中位应答时间为14.5天。在不同的配置文件中观察到了反应，包括单个或多个受影响的谱系，主要或次要计时，和潜在的免疫介导或感染后病理生理学与特发性起源。MSC输注后存活患者的中位随访时间为85个月，53%的患者还活着。值得注意的是,未报告与MSC治疗相关的不良事件.
结论：总之，顺序输注第三方MSCs是一种可行且安全的治疗选择，在allo-SCT后出现血细胞减少症的患者表现出潜在的益处。
