脐带间充质干细胞治疗糖皮质激素耐药的严重型急性移植物抗宿主病19例分析  

Clinical study of umbilical cord-derived mesenchymal stem cells for treatment of nineteen patients with steroid-resistant severe acute graft-versus-host disease

作　　者：陈广华[1] 杨婷[2] 田竤[1] 乔曼[1] 刘慧文[1] 傅琤琤[1] 苗瞄[1] 金正明[1] 唐晓文[1] 韩悦[1] 何广胜[1] 张旭辉[1] 马骁[1] 陈峰[1] 胡晓慧[1] 薛胜利[1] 王荧[1] 仇慧英[1] 孙爱宁[1] 陈志哲[2] 吴德沛[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所；卫生部血栓与止血重点实验室,215006 [2]福建医科大学附属协和医院血液科

出　　处：《中华血液学杂志》2012年第4期303-306,共4页Chinese Journal of Hematology

基　　金：江苏高校优势学科建设工程资助项目;福建省科技厅重点项目（2009Y0022）;新药研究开发关键技术研究项目（2009ZX09503）

摘　　要：目的观察糖皮质激素耐药的严重型急性移植物抗宿主病（aGVHD）患者接受脐带间充质干细胞输注治疗的安全性与疗效。方法19例糖皮质激素耐药的严重型aGVHD患者接受脐带间充质干细胞输注治疗。对患者进行随访观察治疗反应、移植相关死亡、输注相关不良事件和复发率。结果19例患者发生Ⅱ度aGVHD2例，Ⅲ度aGVHD5例，Ⅳ度aGVHD12例，以Ⅲ度和Ⅳ度为主。平均脐带间充质干细胞输注总剂量为2．13（0．60～7．20）×10^6／kg。每次输注细胞总数为3×10^7，7例患者输注1次，2例患者输注2次，10例患者输注3次及以上。11例获得完全缓解，4例获得部分缓解，4例无效。未观察到脐带间充质干细胞输注相关的不良反应，无患者发生间充干细胞相关肿瘤。11例存活，8例死亡，其中4例死于aGVHD、1例死于感染、2例死于aGVHD伴感染、1例死于白血病复发。新鲜制备脐带间充质干细胞锥虫蓝染色细胞活力平均为93％（92％-95％），经程控降温液氮冻存37℃水浴复苏细胞活力平均为72％（70％～74％）。结论输注体外培养扩增的脐带间充质干细胞是糖皮质激素耐药的难治性aGVHD的有效治疗措施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。Objective To evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cells （MSCs） infusion in patients with steroid-resistant severe acute graft-versus-host disease （aGVHD）. Methods A total of 19 patients with steroid-resistant severe aGVHD received MSCs infusion treatment. The treatment response, transplantation-related mortality, events associated with infusion and relapse rate were analyzed. Results Two patients with grade H , 5 patients with grade 11[ and 12 patients with grade IV aGVHD received a total of 58 infusions of MSCs. The mean total dose of MSCs was 2.13 （ range 0.60 -7.20） × 10^6 cells per kg bodyweight. Seven patients received one infusion, 2 patients received two infusions, and 10 patients received three or more infusions. Eleven patients had a complete response and 4 had a partial response and 4 had no response. No patients had side-effects during or immediately after infusions, and no MSCs related tumorigenesis was detected to date. Eleven patients survived and 8 died, 4 for aGVHD, 1 for infection and 2 for aGVHD with concomitant infection and 1 for underlying leukemia relapse. The cell viability of freshly prepared MSCs is 93% （92% -95% ） by trypan blue staining. The cell viability of programmatically frozen and thawed MSCs is 72% （70% - 74% ）. Conclusion Infusion of umbilical cord-derived MSCs expanded in vitro is an effective therapy for patients with steroid-resistant severe aGVHD without negative impact on relapse. Freshly prepared MSCs are superior to frozen and thawed cells in terms of cell viability.

关 键 词：间质干细胞 移植物抗宿主病 造血干细胞移植 复发 

分 类 号：R55[医药卫生—血液循环系统疾病]