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间充质基质细胞治疗急性类固醇难治性移植物抗宿主病:临床反应和长期结果

Mesenchymal Stromal Cells for Treatment of Acute Steroid-Refractory Graft Versus Host Disease: Clinical Responses and Long-Term Outcome.

作者信息

von Dalowski Felix, Kramer Michael, Wermke Martin, Wehner Rebekka, Röllig Christoph, Alakel Nael, Stölzel Friedrich, Parmentier Stefani, Sockel Katja, Krech Mathias, Schmitz Marc, Platzbecker Uwe, Schetelig Johannes, Bornhäuser Martin, von Bonin Malte

机构信息

Medizinische Klinik und Poliklinik I, Universitäts KrebsCentrum, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Universitäts KrebsCentrum, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

出版信息

Stem Cells. 2016 Feb;34(2):357-66. doi: 10.1002/stem.2224. Epub 2015 Oct 13.

DOI:10.1002/stem.2224
PMID:26418955
Abstract

Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Steroid-resistant aGvHD is associated with poor outcome, and no commonly accepted salvage therapy is available for its treatment. Here, we report 58 adult patients treated with mesenchymal stromal cells (MSCs) as salvage therapy for steroid-refractory aGvHD. Third-party MSCs expanded in platelet lysate-containing medium were transfused at a median dose of 0.99 × 10(6) cells per kg b.wt. A median of two MSC infusions were administered to each patient. Median time between the onset of aGvHD and the first infusion of MSCs was 12 days (range, 6-62 days). Most patients (79%) had grade IV aGvHD. Five patients showed complete response, five showed very good partial response, 17 showed partial response, and 31 showed no response. The estimated probability of survival after 1 year was 19%, and median survival was 69 days. Overall survival was not significantly different from that of a historical cohort of patients receiving alternative salvage therapy and no MSC infusions. In conclusion, MSC treatment on top of conventional immunosuppression was associated with an overall response rate of 47% but improved outcome in terms of survival remains to be shown.

摘要

急性移植物抗宿主病(aGvHD)仍然是异基因造血干细胞移植后发病和死亡的主要原因。类固醇难治性aGvHD与不良预后相关,目前尚无普遍接受的挽救治疗方法。在此,我们报告了58例成年患者接受间充质基质细胞(MSCs)作为类固醇难治性aGvHD的挽救治疗。在含血小板裂解物的培养基中扩增的第三方MSCs以每千克体重0.99×10⁶个细胞的中位剂量输注。每位患者中位接受两次MSCs输注。aGvHD发病与首次输注MSCs之间的中位时间为12天(范围6 - 62天)。大多数患者(79%)患有IV级aGvHD。5例患者完全缓解,5例非常好的部分缓解,17例部分缓解,31例无反应。1年后的估计生存概率为19%,中位生存期为69天。总体生存率与接受替代挽救治疗且未输注MSCs的历史队列患者无显著差异。总之,在传统免疫抑制基础上加用MSC治疗的总体缓解率为47%,但在生存方面改善结局仍有待证实。

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