Zhen Sisi, Liu Li, Liu Futong, Shen Yuyan, Zhang Tingting, Fan Yuping, Cui Yuqing, Pan Ling, Liang Chen, Cao Yigeng, Cao Wenbin, Wei Jialin, Zhai Weihua, Chen Xin, Ma Qiaoling, Zhang Rongli, Yang Donglin, He Yi, Pang Aiming, Han Mingzhe, Jiang Erlie, Feng Sizhou
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Hematopoietic Stem Cell Transplantation Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P. R. China.
Tianjin Institutes of Health Science, Tianjin, P. R. China.
Br J Haematol. 2025 Sep;207(3):965-976. doi: 10.1111/bjh.70016. Epub 2025 Jul 21.
Letermovir (LTV) effectively prevents cytomegalovirus (CMV) reactivation in CMV-seropositive patients. To evaluate the impact of LTV in matched sibling haematopoietic stem cell transplantation (HSCT) recipients, we retrospectively compared 72 matched sibling transplantation recipients receiving LTV with 134 controls. LTV significantly reduced 200-day CMV viraemia incidence (5.6% vs. 33.3%, p < 0.001). Multivariable analysis identified anti-thymocyte globulin (ATG) use (p = 0.005) and grade III-IV acute graft-versus-host disease (aGVHD; p < 0.001) as independent risk factors for CMV viraemia, while CMV serostatus did not significantly affect CMV viraemia (p = 0.448). Stratification based on risk factors (ATG, grade III-IV aGVHD) showed that LTV had a more significant effect on high-risk patients compared to low-risk patients. Also, LTV prophylaxis was associated with increased Epstein-Barr virus (EBV) viraemia (13.9% vs. 1.4%, p = 0.025) and higher CD20 monoclonal antibody utilization (11.1% vs. 1.4%, p = 0.046). Long-term survival remained similar between both groups. Results were validated in a second cohort from our centre. In conclusion, LTV prophylaxis significantly reduced CMV viraemia, especially in high-risk patients (ATG/grade III-IV aGVHD). However, the LTV group showed an elevated risk of EBV-related complications. Risk stratification-rather than CMV serostatus alone-should guide CMV prevention strategies in matched sibling HSCT. Larger clinical studies are needed for validation.
来特莫韦（LTV）可有效预防巨细胞病毒（CMV）血清学阳性患者的CMV再激活。为评估LTV在配对同胞造血干细胞移植（HSCT）受者中的影响，我们回顾性比较了72例接受LTV的配对同胞移植受者与134例对照者。LTV显著降低了200天CMV病毒血症的发生率（5.6%对33.3%，p<0.001）。多变量分析确定使用抗胸腺细胞球蛋白（ATG）（p=0.005）和III-IV级急性移植物抗宿主病（aGVHD；p<0.001）为CMV病毒血症的独立危险因素，而CMV血清状态对CMV病毒血症无显著影响（p=0.448）。基于危险因素（ATG、III-IV级aGVHD）进行分层显示，与低风险患者相比，LTV对高风险患者的影响更为显著。此外，LTV预防与爱泼斯坦-巴尔病毒（EBV）病毒血症增加（13.9%对1.4%，p=0.025）和更高的CD20单克隆抗体使用率（11.1%对1.4%，p=0.046）相关。两组的长期生存率相似。我们中心的第二个队列验证了结果。总之，LTV预防显著降低了CMV病毒血症，尤其是在高风险患者（ATG/III-IV级aGVHD）中。然而，LTV组显示出EBV相关并发症的风险升高。在配对同胞HSCT中，应根据风险分层而非单纯的CMV血清状态来指导CMV预防策略。需要更大规模的临床研究进行验证。
