PDF(Pubmed)
Abstract：
Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.
摘要：
慢性移植物抗宿主病（cGVHD）是异基因造血干细胞移植的长期并发症，与生活质量差，发病率和死亡率增加有关。目前,对于对类固醇无反应的患者，有几种批准的治疗方法，如鲁索替尼。然而，相当比例的患者二线治疗失败，这表明需要新的方法。间充质干细胞（MSC）被认为是类固醇难治性cGVHD的潜在治疗方法。评价MSCs反复输注的安全性和有效性,在一项前瞻性I期临床试验中,我们每两周对10例重度类固醇难治性cGVHD患者进行静脉内MSCs.每位患者总共接受了四剂，每个剂量包含来自相同供体和相同传代的1×106个细胞/kg体重。在每次访视期间，使用2014年美国国立卫生研究院（NIH）反应标准评估患者对治疗的反应。纳入了10名不同器官受累的患者，按计划共接受40次输液。值得注意的是,MSC输注耐受性良好,无严重不良事件.初始MSC输注后八周，所有10例患者均表现出部分缓解，其特征是临床症状改善和生活质量提高。总有效率为60%，在最后一次随访时，完全缓解率为20％，部分缓解（PR）率为40％。总生存率为80%,中位随访时间为381天。两名患者因原发疾病复发而死亡。免疫分析显示炎症标志物减少，包括抑制致瘤性2（ST2），C-X-C基序趋化因子配体（CXCL）10和分泌磷蛋白1（SPP1），在MSC治疗之后。反复输注MSC被证明是可行和安全的，它们可能是类固醇难治性cGVHD患者的有效挽救疗法。未来需要进一步的大规模临床研究和长期随访，以确定MSCs在cGVHD中的作用。
