CAJ | 학술논문

目的探讨体外扩增的巨细胞病毒(CMV)特异性细胞毒性T淋巴细胞(CMV-CTL)在难治复发性巨细胞病毒感染患者中的疗效及安全性.方法给予28例难治复发性CMV感染患者输注CMV-CTL,其中19例患者CMV-CTL来自造血干细胞移植原供者,9例来自第三方供者.第1疗程输注1～2次,观察疗效和副作用;第1疗程完全缓解(CR)后复发的患者给予第2疗程治疗,输注1～2次.结果 21例CMV血症患者和7例CMV病患者接受CMV-CTL治疗,首次输注CTL中位治疗时间为移植后76(39 ～321)d,CTL输注中位细胞数为1.0(0.5～10.0)×10 7.第1疗程后,21例CMV血症患者和4例CMV病患者获得CR,CMV血症CR率为100％,CMV病CR率为4/7;获得CR的中位时间分别为首次CTL输注后9(3～23)d和7(4～18)d.6例CMV血症患者和1例CMV病患者CR后复发而给予第2疗程治疗,其中4例CMV血症患者和1例CMV病患者获得CR.5例次患者输注后出现移植物抗宿主病,均为轻中度皮肤受累.随访中6例死于CMV感染,2例死于其他移植后并发症.结论初步结果显示,体外扩增的CMV-CTL输注治疗难治复发性CMV感染安全有效,但输注方案有待进一步完善.
목적 탐토체외확증적거세포병독(CMV)특이성세포독성T림파세포(CMV-CTL)재난치복발성거세포병독감염환자중적료효급안전성.방법 급여28례난치복발성CMV감염환자수주CMV-CTL,기중19례환자CMV-CTL래자조혈간세포이식원공자,9례래자제삼방공자.제1료정수주1～2차,관찰료효화부작용;제1료정완전완해(CR)후복발적환자급여제2료정치료,수주1～2차.결과 21례CMV혈증환자화7례CMV병환자접수CMV-CTL치료,수차수주CTL중위치료시간위이식후76(39 ～321)d,CTL수주중위세포수위1.0(0.5～10.0)×10 7.제1료정후,21례CMV혈증환자화4례CMV병환자획득CR,CMV혈증CR솔위100％,CMV병CR솔위4/7;획득CR적중위시간분별위수차CTL수주후9(3～23)d화7(4～18)d.6례CMV혈증환자화1례CMV병환자CR후복발이급여제2료정치료,기중4례CMV혈증환자화1례CMV병환자획득CR.5례차환자수주후출현이식물항숙주병,균위경중도피부수루.수방중6례사우CMV감염,2례사우기타이식후병발증.결론 초보결과현시,체외확증적CMV-CTL수주치료난치복발성CMV감염안전유효,단수주방안유대진일보완선.
Objective To explore the efficacy and safety of expanding cytomegalovirus specific cytotoxic T lymphocytes (CMV-CTL) in vitro on refractory cytomegalovirus(CMV) infection.Methods A total of twenty-eight patients with refractory CMV infection following stem cell transplant (SCT) were treated with CMV-specific T cells,of which 19 cases were from hematopoietic stem cell donors and 9 from thirdparty donors.In the first course,CTL was infused once or twice and the efficacy and adverse effects were evaluated.If CMV infection relapsed after complete remission (CR),the second course would be given.Results Twenty-one patients with refractory CMV viremia and seven with CMV diseases were eligible for adoptive T-cell transfer.After a median of 76 (39-321) days post-transplant,patients received a median dose of 1.0 (0.5-10.0) × 107 CTL infusion in the first course.All twenty-one patients with CMV viremia and four patients with CMV diseases achieved CR after using 9 (3-23)and 7 (4-18)days respecitvely.Six patients with CMV viremia and one with CMV disease received the second course after recurrence.Another four patients with viremia and one with CMV disease had reached CR again.Five patients exhibited graftversus-host diseases(GVHD),all experiencing mild to moderate skin involvement.Six patients died of CMV infection and 2 of other transplantation-related complications.Conclusion Our preliminary results have shown that CMV-CTL infusion is effective against refractory cytomegalovirus infection following SCT,but therapeutic schedule still needs to be improved in further study.