Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation "MSC-FFM"-Outcome Report of 92 Patients
Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation "MSC-FFM"-Outcome Report of 92 Patients
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DOI：
10.3390/cells8121577
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发表时间：
2019-12-01
期刊：
影响因子：
6
通讯作者：
Bader, Peter
中科院分区：
文献类型：
--
作者：
Bonig, Halvard;Kuci, Zyrafete;Bader, Peter
(1)背景：难治性急性移植物抗宿主病（R-aGvHD）仍然是异基因干细胞移植后死亡的主要原因。目前四年后的存活率为15%;死亡仅部分是由于aGvHD本身，但主要是由于用免疫抑制剂进行R-aGvHD治疗的不良反应，因为这些使患者易于发生机会性感染和移植物抗白血病监测的丧失，导致复发。来自不同组织的间充质基质细胞（MSC）和通过各种方案产生的间充质基质细胞已被提出作为R-aGvHD的补救措施，但最初报告所引起的热情尚未普遍再现。(2)研究方法：我们以前报道过一种独特的MSC产品，它是由多个第三方供体的合并骨髓单核细胞产生的。与来自相同供体的单独扩增的MSC相比，产物显示出剂量间的等效力和更大的免疫抑制能力。该产品MSC-FFM已进入德国的临床常规，并获得国家医院豁免许可。我们以前报告了令人满意的初步临床结果，我们现在正在更新。在我们的批准后药物警戒计划中收集数据，即，这不是一项临床研究，数据是高水平的，未监测。(3)结果如下：报告了92例MSC-FFM接受者的随访，88例GvHD ≥ III度，三分之一仅为类固醇难治性，三分之二为治疗耐药（类固醇难治性加≥ 2线额外治疗）。MSC-FFM中位剂量为3次，无明显毒性。第一次和最后一次评估的总体应答率分别为82%和81%。在6个月时，估计总生存率为64%，而基础疾病的累积死亡率为3%。(4)结论：MSC-FFM有望成为治疗重度R-aGvHD的一种安全有效的方法。
(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD >=degrees III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus >= 2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.