间充质干细胞作为难治性急性移植物抗宿主病挽救性治疗的临床观察  

Clinical observation of mesenchymal stem cell as salvage treatment for refractory acute graft-versus-host disease

作　　者：赵珂[1] 黄芬[1] 彭延文[1] 周红升[1] 范志平[1] 张贤[1] 郭绪涛[1] 许娜[1] 孙竞[1] 项鹏[1] 刘启发[1] 

机构地区：[1]南方医科大学南方医院血液科,广州510515

出　　处：《中华血液学杂志》2013年第2期122-126,共5页Chinese Journal of Hematology

基　　金：国家863课题（2011AA020105）;国家自然科学基金（30971300、81000231）;高等学校博士学科点专项科研基金（20104433110003）;广东省科技计划重点项目（2009A03020007）

摘　　要：目的探讨间充质干细胞（MSC）对二线药物治疗无效的难治性急性移植物抗宿主病（aGVHD）的疗效。方法22例二线药物治疗无效的难治性aGVHD患者在一线和（或）二线免疫抑制剂治疗基础上联合MSC治疗。22例患者在aGVHD发生后中位时间19（11～49）d接受体外扩增的第三方供者骨髓来源的MSC治疗，每次MSC1×10^6／kg、每周1次，连用4次无效者停用。在MSC治疗前、治疗后第4周应用流式细胞术检测患者外周血CD3^＋CD4^＋、CD3^＋CD8^＋及CD4^＋CD25^＋调节T细胞（Treg细胞）的比例。结果22例患者每例MSC中位输注2．5（1～7）次、MSC中位数为4．8（2．5～6．3）×10^612例获得完全缓解、4例部分缓解，总缓解率为72．7％。移植后中位随访时间246．5（36～1116）d。11例存活、11例死亡，死亡原因包括GVHD6例、感染3例、白血病复发和移植后淋巴细胞增殖性疾病（PTLD）各1例。MSC输注后第4周CD3^＋CD4^＋／CD3^＋CD8^＋细胞比例较治疗前显著增高（1．58±0．54对0．494-0．19，t=0．628，P：0．040），调节性T细胞（CIM^＋CD25^＋细胞）与治疗前相比无明显改变（P=0．606）。结论第三方骨髓来源的MSC对于二线药物治疗无效的难治性aGVHD患者具有一定疗效，其作用机制可能与改变CD3^＋CD4^＋／CD3^＋CD8^＋细胞比例有关。Objective To explore the effect of mesenchymal stem cells （MSCs） on refractory acute graft-versus-host disease （GVHD） failed to second-line immunosuppressive therapy. Methods Twenty-two patients with refractory aGVHD received the treatment of first - and/or second - line immunosuppressive a- gents in combination with MSCs. The MSCs from bone marrow （ BM ） of HLA-unrelated third-party donors, were used at the median time of 19 （11 -49）days after aGVHD onset, at a dose of 1 × 10^6/kg once with an interval of 14 days. If the symptoms of aGVHD did not improve after continuous infusion four times, MSCs would be discontinued. Meanwhile the proportion of CD3 ^＋ CIM^＋ ,CD3 ^＋ CD8^＋ and CIM^＋ CD25^＋ was detected by flow cytometry （FCM） before and 4 weeks after the MSCs infusion. Results The median dose of MSC was 4.8 （2.5- 6.3） × 10^6cell ·kg^-1 with a median infusion of 2.5 （1 -7） times per case. Twelve patients a- chieved complete response （ CR ）, four partial response （ PR ） after treatment. The total effective rate was 72.7% （16/22）. With a median follow-up of 246.5 （36 - 1116） days post-transplantation, 11 patients sur- vived and 11 died. The causes of death inelued GVHD （ n = 6）, infections （ n = 3 ）, leukemia relapse （ n = 1 ） and post - transplant lymphoproliferative diseases（ n = 1 ）, respectively. The proportion of CD3^＋ C1M ＋/CD3^＋ CD8^＋ was significantly higher at 4th week after MSCs infusion compared to before infusion （ 1.58 ± 0.54 vs 0.49 ±0.19 ,t =0.628 ,P =0.04）. The number of CD4^＋ CD25^＋ Treg cells had not changed much compared to before infusion（P = 0. 606）. Conclusion MSCs derived from the BM of a third-party donor are effective to treat aGVHD failed to second-line immunosuppressive therapy after allo-HSCT. MSCs might play a role in aGVHD by regulating the rate of CD3^＋ CD4^＋/CD3^＋ CD8^＋ .

关 键 词：移植物抗宿主病 间质干细胞 造血干细胞移植 

分 类 号：R457.7[医药卫生—治疗学]