Adult Human Mesenchymal Stem Cells Added to Corticosteroid Therapy for the Treatment of Acute Graft-versus-Host Disease
Adult Human Mesenchymal Stem Cells Added to Corticosteroid Therapy for the Treatment of Acute Graft-versus-Host Disease
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DOI：
10.1016/j.bbmt.2008.03.012
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发表时间：
2009-07-01
影响因子：
4.3
通讯作者：
Uberti, Joseph
中科院分区：
文献类型：
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作者：
Kebriaei, Partow;Isola, Luis;Uberti, Joseph
间充质干细胞（MSCs）独特的免疫调节特性使其成为研究移植物抗宿主病（GVHD）的基本药物。人类间充质干细胞用于治疗新生急性GVHD （aGVHD）。II-IV级GVHD患者随机接受2种人间充质干细胞（Prochymal (R)）治疗，剂量为200万或800万间充质干细胞/kg，联合皮质类固醇。患者接受他克莫司、环孢素（CsA）或霉酚酸酯（MMF）预防GVHD。研究终点包括Prochymal给药的安全性、对Prochymal的诱导反应、aGVHD第28天的总体反应和长期安全性。纳入32例患者，其中31例可评估：男性21例，女性10例；中位年龄52岁（范围：34-67岁）。11级21例，111级8例，IV级3例。94%的患者对Prochymal有初始反应（77%完全缓解[CR]， 16%部分缓解[PR]）。没有输注毒性或异位组织形成的报道。低剂量和高剂量的原胺在安全性和有效性方面没有差异。综上所述，Prochymal可以安全地输注到aGVHD患者体内，并在高比例的GVHD患者中引起反应。
The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them a rationale agent to investigate for graft-versus-host disease (GVHD). Human MSCs were used to treat de novo acute GVHD (aGVHD). Patients with grades II-IV GVHD were randomized to receive 2 treatments of human MSCs (Prochymal (R)) at a dose of either 2 or 8 million MSCs/kg in combination with corticosteroids. Patients received GVHD prophylaxis with tacrolimus, cyclosporine, (CsA) or mycophenolate mofetil (MMF). Study end-points included safety of Prochymal administration, induction of response to Prochymal, and overall response of aGVHD by day 28, and long-term safety. Thirty-two patients were enrolled, with 31 evaluable: 21 males, 10 females; median age 52 years (range: 34-67). Twenty-one patients had grade 11, 8 had grade 111, and 3 had grade IV aGVHD. Ninety-four percent of patients had an initial response to Prochymal (77% complete response [CR] and 16% partial response [PR]). No infusional toxicities or ectopic tissue formations were reported. There was no difference with respect to safety or efficacy between the low and high Prochymal dose. In conclusion, Prochymal can be infused safely into patients with aGVHD and induces response in a high proportion of GVHD patients.