Efficacy and Safety of Letermovir for Cytomegalovirus Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-06-12 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S513383

Yongbing Zhu, Li Wang, Yu Xiang, Yaqin Wang, Ai Zhang, Yao Wang, Mengmeng Yin, Jianxin Dun, Yuting Xu, Qun Hu, Wen Yu, Aiguo Liu

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Abstract

Purpose: Cytomegalovirus (CMV) infection represents a severe complication following hematopoietic cell transplantation (HCT), resulting in high mortality. The prevention of CMV reactivation is crucial for enhancing patient prognosis post-HCT. Letermovir prophylaxis has effectively reduced the incidence of clinically significant CMV infection (csCMVi) in adult HCT recipients. However, clinical data in pediatric patients remain limited.

Patients and methods: We included 106 children who underwent HCT at our hospital between March 2019 and July 2024. The patients were grouped based on whether or not they received letermovir prophylaxis. By analyzing their general characteristics and laboratory findings, exploring the risk factors of csCMVi, and assessing the efficacy and safety of letermovir in pediatric patients.

Results: Among the 106 patients, all patients were at high risk for CMV reactivation. Forty-four received letermovir prophylaxis, while 62 did not. CsCMVi occurred in 45 patients, with a significantly lower incidence in the letermovir group compared to the control group (5 [11.3%] vs 40 [64.5%], p < 0.001). Umbilical cord blood (UCB) was used in 7 patients (15.9%) in the letermovir group and in 1 patient in the control group (p < 0.05). There was no statistically significant difference in all-cause mortality between the two groups. Grade II-IV GvHD and the use of letermovir were associated with csCMVi, with letermovir identified as the only independent preventive factor for csCMVi during the first 100 days post-HCT, especially in patients with 4-5 risk factors of csCMVi. In patients with aplastic anemia, the incidence of csCMVi was notably lower in those who received letermovir prophylaxis. No patients in the study withdrew from treatment due to adverse reactions.

Conclusion: Letermovir is both effective and safe for CMV prophylaxis in pediatric patients following HCT, especially in patients with more risk factors of csCMVi. Grade II-IV GvHD increases the risk of csCMVi, while letermovir prophylaxis reduces the risk.

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莱特莫韦预防小儿异体造血干细胞移植后巨细胞病毒的疗效和安全性。

目的：巨细胞病毒（CMV）感染是造血细胞移植（HCT）后的严重并发症，导致高死亡率。预防巨细胞病毒再激活对提高hct后患者预后至关重要。雷特莫韦预防有效地降低了成人HCT受者临床显著巨细胞病毒感染（csCMVi）的发生率。然而，儿科患者的临床数据仍然有限。患者和方法：我们纳入了2019年3月至2024年7月期间在我院接受HCT治疗的106名儿童。患者根据是否接受雷替韦预防治疗进行分组。通过分析他们的一般特征和实验室结果，探讨csCMVi的危险因素，评估莱特莫韦在儿科患者中的疗效和安全性。结果：在106例患者中，所有患者都有CMV再激活的高风险。44人接受了利特莫韦预防治疗，62人没有。45例患者发生CsCMVi，与对照组相比，letermovir组的发病率显著降低（5例[11.3%]vs 40例[64.5%],p < 0.001）。letermovir组7例（15.9%）使用脐带血，对照组1例（p < 0.05）。两组的全因死亡率无统计学差异。II-IV级GvHD和letermovir的使用与csCMVi相关，在hct后的前100天内，letermovir被确定为唯一独立的csCMVi预防因素，特别是在具有4-5个csCMVi危险因素的患者中。在再生障碍性贫血患者中，接受莱替韦预防的csCMVi发病率明显较低。本研究中没有患者因不良反应退出治疗。结论：Letermovir对HCT后的儿童CMV预防有效且安全，特别是对csCMVi危险因素较多的患者。II-IV级GvHD增加csCMVi的风险，而莱替韦预防可降低风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.