中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2013年
2期
122-126
,共5页
赵珂%黄芬%彭延文%周红升%范志平%张贤%郭绪涛%许娜%孙竞%项鹏%刘启发
趙珂%黃芬%彭延文%週紅升%範誌平%張賢%郭緒濤%許娜%孫競%項鵬%劉啟髮
조가%황분%팽연문%주홍승%범지평%장현%곽서도%허나%손경%항붕%류계발
移植物抗宿主病%间质干细胞%造血干细胞移植
移植物抗宿主病%間質榦細胞%造血榦細胞移植
이식물항숙주병%간질간세포%조혈간세포이식
Graft-versus-host disease%Mesenchymal stem cell%Hematopoietic stem cell transplantation
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MSC 1×106/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)×106.12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GVHD 6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0.49±0.19,t=0.628,P=0.040),调节性T细胞(CD4+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.
目的 探討間充質榦細胞(MSC)對二線藥物治療無效的難治性急性移植物抗宿主病(aGVHD)的療效.方法 22例二線藥物治療無效的難治性aGVHD患者在一線和(或)二線免疫抑製劑治療基礎上聯閤MSC治療.22例患者在aGVHD髮生後中位時間19(11~49)d接受體外擴增的第三方供者骨髓來源的MSC治療,每次MSC 1×106/kg、每週1次,連用4次無效者停用.在MSC治療前、治療後第4 週應用流式細胞術檢測患者外週血CD3+CD4+、CD3+CD8+ 及CD4+CD25+調節T細胞(Treg細胞)的比例.結果 22例患者每例MSC中位輸註2.5(1~7)次、MSC中位數為4.8(2.5~6.3)×106.12例穫得完全緩解、4例部分緩解,總緩解率為72.7%.移植後中位隨訪時間246.5(36~1116)d.11例存活、11例死亡,死亡原因包括GVHD 6例、感染3例、白血病複髮和移植後淋巴細胞增殖性疾病(PTLD)各1例.MSC輸註後第4週CD3+CD4+/CD3+CD8+細胞比例較治療前顯著增高(1.58±0.54對0.49±0.19,t=0.628,P=0.040),調節性T細胞(CD4+CD25+細胞)與治療前相比無明顯改變(P=0.606).結論 第三方骨髓來源的MSC對于二線藥物治療無效的難治性aGVHD患者具有一定療效,其作用機製可能與改變CD3+CD4+/CD3+CD8+細胞比例有關.
목적 탐토간충질간세포(MSC)대이선약물치료무효적난치성급성이식물항숙주병(aGVHD)적료효.방법 22례이선약물치료무효적난치성aGVHD환자재일선화(혹)이선면역억제제치료기출상연합MSC치료.22례환자재aGVHD발생후중위시간19(11~49)d접수체외확증적제삼방공자골수래원적MSC치료,매차MSC 1×106/kg、매주1차,련용4차무효자정용.재MSC치료전、치료후제4 주응용류식세포술검측환자외주혈CD3+CD4+、CD3+CD8+ 급CD4+CD25+조절T세포(Treg세포)적비례.결과 22례환자매례MSC중위수주2.5(1~7)차、MSC중위수위4.8(2.5~6.3)×106.12례획득완전완해、4례부분완해,총완해솔위72.7%.이식후중위수방시간246.5(36~1116)d.11례존활、11례사망,사망원인포괄GVHD 6례、감염3례、백혈병복발화이식후림파세포증식성질병(PTLD)각1례.MSC수주후제4주CD3+CD4+/CD3+CD8+세포비례교치료전현저증고(1.58±0.54대0.49±0.19,t=0.628,P=0.040),조절성T세포(CD4+CD25+세포)여치료전상비무명현개변(P=0.606).결론 제삼방골수래원적MSC대우이선약물치료무효적난치성aGVHD환자구유일정료효,기작용궤제가능여개변CD3+CD4+/CD3+CD8+세포비례유관.
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 agents 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 1×106/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+CD4+、CD3+CD8+ and CD4+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)×106cell·kg-1 with a median infusion of 2.5(1-7) times per case. Twelve patients achieved 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 survived and 11 died. The causes of death inclued GVHD(n=6), infections(n=3), leukemia relapse(n=1) and post-transplant lymphoproliferative diseases(n=1), respectively. The proportion of CD3+CD4+/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+.
