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更昔洛韦治疗异基因造血干细胞移植后巨细胞病毒感染:有效临床应用的技巧与提示。

Letermovir for cytomegalovirus infection in allogeneic hematopoietic stem-cell transplantation: tips and notes for effective use in clinical practice.

机构信息

Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

Expert Rev Anti Infect Ther. 2024 Apr;22(4):169-178. doi: 10.1080/14787210.2024.2322439. Epub 2024 Mar 1.

Abstract

INTRODUCTION

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While conventional antiviral agents such as ganciclovir can be used for CMV prophylaxis, toxicities such as myelosuppression are a major concern.

AREA COVERED

This work aimed to summarize the latest information and practical issues regarding a new anti-CMV agent, letermovir (LET).

EXPERT OPINION

LET inhibits CMV replication by binding to components of the DNA terminase complex. A phase 3 trial in allo-HSCT recipients showed a reduced incidence of clinically significant CMV infection in the LET group. In 2017, this agent was first approved for CMV prophylaxis in adult CMV-seropositive allo-HSCT recipients in the United States, and is now used worldwide. While LET has an excellent toxicity profile, there are issues to be aware of, such as interactions with other drug classes (e.g. immunosuppressants and antifungals) and reactivation of CMV infection following LET cessation. While LET is the current standard of care for CMV prophylaxis, there are no established protocols for preemptive treatment of asymptomatic CMV viremia or for treatment of developed CMV disease. Further research is needed to maximize the benefits of LET, including the discovery of biomarkers.

摘要

简介

巨细胞病毒(CMV)感染仍然是异基因造血干细胞移植(allo-HSCT)后的主要并发症。虽然传统的抗病毒药物如更昔洛韦可用于 CMV 预防,但骨髓抑制等毒性是一个主要问题。

涵盖领域

本工作旨在总结新型抗 CMV 药物乐他脒(LET)的最新信息和实际问题。

专家意见

LET 通过与 DNA 端酶复合物的成分结合来抑制 CMV 复制。一项 allo-HSCT 受者的 3 期试验显示 LET 组临床显著 CMV 感染的发生率降低。2017 年,该药物首次在美国被批准用于 CMV 阳性的成人 allo-HSCT 受者的 CMV 预防,现已在全球使用。虽然 LET 的毒性谱极佳,但仍需注意一些问题,例如与其他药物类别(如免疫抑制剂和抗真菌药)的相互作用,以及 LET 停药后 CMV 感染的再激活。虽然 LET 是 CMV 预防的当前标准治疗方法,但对于无症状 CMV 病毒血症的抢先治疗或已发生的 CMV 疾病的治疗尚无既定方案。需要进一步研究以最大限度地发挥 LET 的益处,包括发现生物标志物。

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