脐带间充质干细胞辅助治疗糖皮质激素耐药的慢性移植物抗宿主病5例并文献复习

目的:探讨脐带间充质干细胞输注治疗糖皮质激素耐药的慢性移植物抗宿主病的疗效和安全性。方法:5例糖皮质激素耐药的慢性移植物抗宿主病患者在原有免疫抑制剂治疗基础上联合脐带间充质干细胞治疗,2~4次为1个疗程,每次间隔1周。对患者进行定期随访观察其治疗效果、移植相关死亡、输注相关不良事件和复发率。结果:5例患者接受脐带间充质干细胞输注后2例获得完全缓解(CR)、2例获得部分缓解(PR),1例患者死亡。2例CR患者分别在脐带间充质干细胞治疗368、452d后停用免疫抑制剂,随访1~1.5年慢性移植物抗宿主病无复发;2例PR患者在脐带间充质干细胞治疗84、96d后开始进入免疫抑制剂减量阶段,目前病情仍稳定并存活。1例患者死于原发病无复发性肺部严重感染。治疗过程中及治疗后未观察到与治疗有关的副作用。新鲜制备脐带间充质干细胞的细胞活力(92%~95%)高于液氮冻存37℃水浴复苏细胞活力(72%~76%)。结论:脐带间充质干细胞辅助治疗可以改善糖皮质激素耐药的慢性移植物抗宿主病的临床症状且不增加恶性血液病复发率,新鲜制备间充质干细胞活性高于液氮冻存复苏细胞。

Umbilical Cord Mesenchymal StemCells for the Treatment of 5 cases ofSteroid-resistant Chronic Graft-versus-host Disease and Literature Review

Objective： To investigate the clinical effect and safety of UC-MSC（umbilical cord mesenchymal stem cells, UC-MSC） transplantation in the treatment of conventional therapy-resistant chronic graft-versus-host disease （GVHD）. Methods： Five patients with steroid-resistant chronic GVHD were received UC-MSC transplantation （2 - 4 times as a course of treatment which every time interval one week） with total cellular number of UC-MSC was 5-7 × 10^7 by intravenous infusion. All patients were followed up regularly after transplantation. The treatment response, transplantation-related mortality, events associated with infusion and relapse rate were analyzed and literature review was performed. Results： After transplantation, the clinical symptoms of all patients were obviously improved. Among 5 patients, 2 patients had complete response（CR）, 2 showed partial response（PR） and 1 died. 2 CR patients discontinued all of the immunosuppressive agents on 368 to 452 days after the UC-MSC infusion and without relapse after followed up 1 to 1.5 years. 2 PR pa-tients decrement all immunosuppressive agents after 84 to 96 days and now the patient＇s condition of the two patients is stable and both patients are alive. All patients had no severe complications and clear side effects during and after transplantation. The cell viability of freshly prepared UC-MSC is higher （92-95%） by trypan blue staining than the cell viability of programmatically frozen and thawed UC-MSC （72-76%）. Conclusion： Infusion of UC-MSC expanded in vitro was an effective therapy for patients with steroid-resistant chronic GVHD without negative impact on relapse. Freshly prepared UC-MSC are superior to frozen and thawed cells in terms of cell vi-ability.