Kaito Satoshi, Nakajima Yujiro, Hara Konan, Toya Takashi, Nishida Tetsuya, Uchida Naoyuki, Mukae Junichi, Fukuda Takahiro, Ozawa Yukiyasu, Tanaka Masatsugu, Ikegame Kazuhiro, Katayama Yuta, Kuriyama Takuro, Kanda Junya, Atsuta Yoshiko, Ogata Masao, Taguchi Ayumi, Ohashi Kazuteru
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Department of Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
Blood Adv. 2020 Mar 24;4(6):1051-1061. doi: 10.1182/bloodadvances.2019000814.
Cytomegalovirus (CMV) infection is a major complication in allogeneic stem cell transplantation. The utility of CMV prophylaxis with letermovir has been reported; however, the specific applications remain unclear. In this study, we retrospectively analyzed large-scale registry data (N = 10 480) to clarify the risk factors for nonrelapse mortality (NRM) in connection with CMV reactivation. First, we identified risk factors for CMV reactivation using multivariate analysis and developed a scoring model. Although the model effectively stratified reactivation risk into 3 groups (43.7% vs 60.9% vs 71.5%; P < .001), the 3-year NRM was significantly higher in patients with CMV reactivation, even in the low (20.9% vs 13.0%, P < .001), intermediate (21.4% vs 15.6%; P < .001), and high (29.3% vs 18.0%; P < .001) reactivation risk groups. Next, survival analysis considering competing risks, time-dependent covariates, and interaction terms for exploring the heterogeneous impact of CMV reactivation on NRM in the training cohort revealed that chronic myeloid leukemia (CML) (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.05-2.96; P = .033), good performance status (PS) (HR, 1.42; 95% CI, 1.04-1.94; P = .028), HLA-matched donor (HR, 1.34; 95% CI, 1.06-1.70; P = .013), and standard-risk disease (HR, 1.28; 95% CI, 1.04-1.58; P = .022) were associated with increased NRM. In the test cohort, CMV reactivation was significantly associated with increased 3-year NRM among patients with 2 to 4 factors (22.1% vs 13.1%; P < .001) but was comparable among patients with 0 or 1 factor (23.2% vs 20.4%; P = .62). We propose that CMV prophylaxis should be determined based on reactivation risk, as well as these other factors.
巨细胞病毒（CMV）感染是异基因干细胞移植中的主要并发症。已有关于使用来特莫韦进行CMV预防的效用的报道；然而，具体应用仍不明确。在本研究中，我们回顾性分析了大规模登记数据（N = 10480），以阐明与CMV再激活相关的非复发死亡率（NRM）的危险因素。首先，我们使用多变量分析确定了CMV再激活的危险因素，并建立了一个评分模型。尽管该模型有效地将再激活风险分为3组（43.7%对60.9%对71.5%；P <.001），但CMV再激活患者的3年NRM显著更高，即使在低（20.9%对13.0%，P <.001）、中（21.4%对15.6%；P <.001）和高（29.3%对18.0%；P <.001）再激活风险组中也是如此。接下来，在训练队列中进行的考虑竞争风险、时间依赖性协变量以及用于探索CMV再激活对NRM的异质性影响的交互项的生存分析显示，慢性髓性白血病（CML）（风险比[HR]，1.76；95%置信区间[CI]，1.05 - 2.96；P =.033）、良好的体能状态（PS）（HR，1.42；95% CI，1.04 - 1.94；P =.028）、HLA匹配的供体（HR，1.34；95% CI，1.06 - 1.70；P =.013）和标准风险疾病（HR，1.28；95% CI，1.04 - 1.58；P =.022）与NRM增加相关。在测试队列中，CMV再激活在有2至4个因素的患者中与3年NRM增加显著相关（22.1%对13.1%；P <.001），但在有0或1个因素的患者中相当（23.2%对20.4%；P =.62）。我们建议应根据再激活风险以及这些其他因素来确定CMV预防措施。
