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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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：肺移植受者患严重巨细胞病毒（CMV）疾病的风险很高。letermovir（LET）的标签外使用可以避免与伐更昔洛韦（VGCV）相关的骨髓毒性，但是肺移植的数据有限。本研究旨在评估肺移植受者LET预防的结果。
方法：本回顾性研究，匹配的队列研究包括肺移植受者,这些受者在VGCV不耐受后接受LET治疗以进行CMV初级预防.患者根据年龄与历史VGCV对照1：1匹配，血清状态组，和移植时间。主要结果是在LET开始后1年内CMV突破；次要结果包括血液学变化。
结果：每组共纳入124例肺移植受者（32%CMV不匹配，D+R-),LET在移植后的中位数为9.6个月。在LET组中观察到一个CMV突破事件（0.8％），而在VGCV组中观察到四个（3.2％）（p=.370）。在LET开始时，白细胞（WBC）计数的中位数（四分位距）为3.1（2.1-5.6），在随访结束时增加到5.1（3.9-7.2）（p<.001）。对于VGCV控件，基线时WBC为4.8（3.4-7.2），随访结束时WBC为5.4（3.6-7.2）；这种差异没有统计学意义（p=0.395）。此外,98.4％的LET患者在LET前一年经历了≥1次白细胞减少症发作，而在开始后一年为71.8％（p<.001）。中性粒细胞减少症也观察到了类似的结果（48.4%和17.7%，p<.001)。
结论：LET预防与CMV再激活和白细胞减少恢复率低相关。LET可能代表不能耐受VGCV的肺移植受体的合理预防选择。
方法：本回顾性研究，匹配的队列研究包括肺移植受者,这些受者在VGCV不耐受后接受LET治疗以进行CMV初级预防.患者根据年龄与历史VGCV对照1：1匹配，血清状态组，和移植时间。主要结果是在LET开始后1年内CMV突破；次要结果包括血液学变化。
结果：每组共纳入124例肺移植受者（32%CMV不匹配，D+R-),LET在移植后的中位数为9.6个月。在LET组中观察到一个CMV突破事件（0.8％），而在VGCV组中观察到四个（3.2％）（p=.370）。在LET开始时，白细胞（WBC）计数的中位数（四分位距）为3.1（2.1-5.6），在随访结束时增加到5.1（3.9-7.2）（p<.001）。对于VGCV控件，基线时WBC为4.8（3.4-7.2），随访结束时WBC为5.4（3.6-7.2）；这种差异没有统计学意义（p=0.395）。此外,98.4％的LET患者在LET前一年经历了≥1次白细胞减少症发作，而在开始后一年为71.8％（p<.001）。中性粒细胞减少症也观察到了类似的结果（48.4%和17.7%，p<.001)。
结论：LET预防与CMV再激活和白细胞减少恢复率低相关。LET可能代表不能耐受VGCV的肺移植受体的合理预防选择。
