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评价乐特韦(letermovir)对比缬更昔洛韦(valganciclovir)用于预防成人肺移植受者巨细胞病毒病的疗效和安全性。

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

机构信息

Department of Pharmacy Services, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.

Division of Transplant Pulmonology, Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.

出版信息

Transpl Infect Dis. 2024 Jun;26(3):e14279. doi: 10.1111/tid.14279. Epub 2024 May 14.

Abstract

BACKGROUND

Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients.

METHODS

This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes.

RESULTS

A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001).

CONCLUSION

LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

摘要

背景

肺移植受者发生严重巨细胞病毒(CMV)疾病的风险很高。莱特莫韦(LET)的超说明书使用可能避免缬更昔洛韦(VGCV)相关的骨髓抑制,但在肺移植中的数据有限。本研究旨在评估肺移植受者中 LET 预防的结果。

方法

本回顾性、匹配队列研究纳入了因不耐受 VGCV 而接受 LET 进行原发性 CMV 预防的肺移植受者。患者按年龄、血清状态组和移植后时间进行 1:1 匹配,与历史 VGCV 对照组匹配。主要结局是 LET 启动后 1 年内 CMV 突破;次要结局包括血液学变化。

结果

每组纳入 124 例肺移植受者(CMV 错配率为 32%,D+R-),LET 启动中位时间为移植后 9.6 个月。LET 组发生 1 例(0.8%)CMV 突破事件,VGCV 组发生 4 例(3.2%)(p=0.370)。LET 组起始时的白细胞(WBC)计数中位数(四分位距)为 3.1(2.1-5.6),随访结束时为 5.1(3.9-7.2)(p<0.001)。VGCV 对照组基线时的 WBC 为 4.8(3.4-7.2),随访结束时为 5.4(3.6-7.2);差异无统计学意义(p=0.395)。此外,在 LET 前一年,98.4%的 LET 患者经历了至少 1 次白细胞减少症发作,而在 LET 后一年,这一比例为 71.8%(p<0.001)。中性粒细胞减少症(48.4%和 17.7%,p<0.001)也有类似的结果。

结论

LET 预防与 CMV 再激活和白细胞减少症恢复率低有关。对于不能耐受 VGCV 的肺移植受者,LET 可能是一种合理的预防选择。

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