脐带间充质干细胞治疗难治性慢性移植物抗宿主病

Umbilical cord mesenchymal stem cells for the treatment of refractory chronic graft-versus-host disease

背景:慢性移植物抗宿主病是造血干细胞移植后最常见的并发症,糖皮质激素是目前一线治疗药物,对于激素耐药型慢性移植物抗宿主病患者联用免疫抑制剂治疗仍有一半患者无效。脐带间充质干细胞免疫原性低,为临床治疗移植物抗宿主病提供了可能。目的:探讨人脐带间充质干细胞治疗难治性慢性移植物抗宿主病的疗效和安全性。方法:15例难治性慢性移植物抗宿主病患者在原有免疫抑制剂的基础上接受脐带间充质干细胞治疗,观察其疗效、输注相关不良反应和存活情况,流式细胞术检测患者外周血淋巴细胞比值变化。该研究经中山大学附属第三医院伦理委员会审批。结果与结论:①15例患者中男12例,女3例,中位发病年龄29(17-52)岁,完全缓解4例,部分缓解7例,总有效11例,无效4例;②脐带间充质干细胞治疗后患者外周血中CD19^+细胞比值有低于治疗前趋势,CD19^+CD27^+、CD3^+细胞比值有高于治疗前趋势,差异无显著性意义;③未观察到脐带间充质干细胞输注相关的不良反应,无原发病复发和间充质干细胞相关的肿瘤;④结果表明脐带间充质干细胞治疗难治性慢性移植物抗宿主病安全有效。

BACKGROUND: Chronic graft-versus-host disease is the most common complication after transplantation and glucocorticoid is a first-line drug. Glucocorticoid in combination with immunosuppressive therapy is not effective in half of the patients with hormone resistant chronic graft-versus-host disease. The low immunogenicity of umbilical cord mesenchymal stem cells provides the possibility for clinical treatment of graft-versus-host disease. OBJECTIVE: To investigate the clinical efficacy and safety of umbilical cord-derived mesenchymal stem cells to treat refractory chronic graft-versus-host disease. METHODS: Fifteen patients with refractory chronic graft-versus-host disease received mesenchymal stem cell infusion treatment based on immunosuppressive therapy. The therapeutic efficacy, infusion-related adverse reactions, and survival were analyzed. The ratio change of peripheral blood lymphocytes was determined by flow cytometry. This study was approved by Medical Ethics Committee, Third Affiliated Hospital of Sun Yat-sen University in China. RESULTS AND CONCLUSION: There were 12 male and 3 female patients with a median age of 29 years(ranging from 17 to 52 years). Four patients obtained complete response, seven patients obtained partial response, 11 had overall response, and four patients had no response. After treatment by umbilical cord mesenchymal stem cells, the ratio of CD19+ cells in the peripheral blood was slightly, but not significantly lower, but CD19+CD27+ and CD3+ cell ratios were slightly, but not significantly higher than those before treatment. No patients had adverse reactions related to infusion of umbilical cord mesenchymal stem cells and no patients had primary disease recurrence and mesenchymal stem cell-related tumor. These findings suggest that umbilical cord-derived mesenchymal stem cell infusion is an effective and safe therapy for refractory chronic graft-versus-host disease.