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用于治疗异基因造血干细胞移植后患者难治性巨细胞病毒感染的巨细胞病毒特异性细胞毒性T淋巴细胞

[Cytomegalovirus specific cytotoxic T lymphocytes for treatment of refractory cytomegalovirus infection in patients following allogeneic hematopoietic stem cell transplantation].

作者信息

Xu Zhengli, Huang Xiaojun, Sun Yuqian, Wang Fengrong, Yan Chenhua, Zhang Xiaohui, Han Wei, Chen Yuhong, Wang Jingzhi, Chen Huan, Wang Yu, Zhang Yuanyuan, Liu Kaiyan, Xu Lanping

机构信息

Institute of Hematology, People's Hospital, Peking University,Beijing 100044, China.

Institute of Hematology, People's Hospital, Peking University,Beijing 100044, China. Email:

出版信息

Zhonghua Nei Ke Za Zhi. 2015 Feb;54(2):101-5.

Abstract

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 third-party 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) × 10(7) 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 graft-versus-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.

摘要

目的

探讨体外扩增巨细胞病毒特异性细胞毒性T淋巴细胞(CMV-CTL)治疗难治性巨细胞病毒(CMV)感染的疗效及安全性。

方法

28例干细胞移植(SCT)后发生难治性CMV感染的患者接受CMV特异性T细胞治疗,其中19例来自造血干细胞供者,9例来自第三方供者。在第一个疗程中,CTL输注1次或2次,并评估疗效和不良反应。若完全缓解(CR)后CMV感染复发,则给予第二个疗程。

结果

21例难治性CMV病毒血症患者和7例CMV疾病患者符合过继性T细胞转移治疗条件。移植后中位76(39 - 321)天,患者在第一个疗程中接受的CTL输注中位剂量为1.0(0.5 - 10.0)×10⁷ 。所有21例CMV病毒血症患者和4例CMV疾病患者分别在使用CTL后9(3 - 23)天和7(4 - 18)天达到CR。6例CMV病毒血症患者和1例CMV疾病患者复发后接受了第二个疗程。另外4例病毒血症患者和1例CMV疾病患者再次达到CR。5例患者出现移植物抗宿主病(GVHD),均有轻度至中度皮肤受累。6例患者死于CMV感染,2例死于其他移植相关并发症。

结论

我们的初步结果表明,CMV-CTL输注对SCT后难治性CMV感染有效,但治疗方案仍需在进一步研究中改进。

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