Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, California.
Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, California.
Biol Blood Marrow Transplant. 2020 Oct;26(10):1963-1970. doi: 10.1016/j.bbmt.2020.07.002. Epub 2020 Jul 9.
Despite effective therapies, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in hematopoietic cell transplant recipients. At particular risk are recipients of alternative grafts such as umbilical cord blood (UCB), haploidentical transplants (haplo), or patients conditioned with T-cell depleting regimens such as anti-thymocyte globulin (ATG). With the approval of letermovir, its impact on high-risk patients is of particular interest. To evaluate the impact of letermovir prophylaxis at our center, we performed a retrospective analysis of 114 high-risk patients who received letermovir as prophylaxis (LET PPX) between January 2018 through December 2019, including 30 UCB and 22 haplo recipients, compared with 637 historical controls with comparable risk between January 2013 and December 2019. By post-transplant day 100 (D+100), letermovir prophylaxis significantly decreased the incidence of both CMV DNAemia compared with controls (45.37% versus 74.1%; P < .001) and clinically significant CMV infection (12.04% versus 48.82%; P < .001). The impact of LET PPX was even more profound on the incidence of clinically significant CMV infection (CSI), defined as the administration of antiviral therapy as preemptive therapy for CMV DNAemia or treatment for CMV disease. CSI was significantly lower in haplo recipients on LET PPX compared with controls (13.64% versus 73.33%; P= .02) and UCB recipients on LET PPX compared with controls (3.45% versus 37.5%; P < .001). No patients on LET primary PPX developed CMV disease in any treatment group by D+100 compared with controls (0% versus 5.34%, respectively; P = .006). Patients on LET PPX had fewer hospitalizations involving initiation of anti-CMV therapy compared with controls (0.93% versus 15.23%, respectively). Our analysis of the largest cohort of patients at high risk for CMV reactivation published to date demonstrates that letermovir prophylaxis significantly reduces the number of patients who receive CMV-active antiviral therapy for either DNAemia or disease due to CMV.
尽管有有效的治疗方法，但巨细胞病毒（CMV）仍然对造血细胞移植受者的发病率和死亡率有重大影响。风险特别高的是接受替代移植物的患者，如脐带血（UCB）、半相合移植（haplo），或接受 T 细胞耗竭方案预处理的患者，如抗胸腺细胞球蛋白（ATG）。随着勒特洛韦的批准，它对高危患者的影响尤其受到关注。为了评估我们中心使用勒特洛韦预防的效果，我们对 2018 年 1 月至 2019 年 12 月期间接受勒特洛韦预防（LET PPX）的 114 例高危患者进行了回顾性分析，其中包括 30 例 UCB 和 22 例 haplo 受者，并与 2013 年 1 月至 2019 年 12 月期间具有可比性风险的 637 例历史对照进行比较。在移植后 100 天（D+100），与对照组相比，勒特洛韦预防显著降低了 CMV DNAemia 的发生率（45.37% 与 74.1%；P<.001）和临床显著 CMV 感染（12.04% 与 48.82%；P<.001）。在 haplo 受者和 UCB 受者中，LET PPX 对临床显著 CMV 感染（CSI）的影响更为显著，CSI 定义为预防性治疗 CMV DNAemia 或治疗 CMV 疾病时开始抗病毒治疗。与对照组相比，haplo 受者和 UCB 受者的 CSI 发生率显著降低（分别为 13.64%和 3.45%与 73.33%和 37.5%；P=0.02 和 P<.001）。与对照组相比（分别为 0%和 5.34%；P=0.006），在任何治疗组中，LET 主要预防组均无患者在 D+100 时发生 CMV 疾病。与对照组相比，接受 LET PPX 治疗的患者因 CMV 而开始抗 CMV 治疗的住院次数更少（分别为 0.93%和 15.23%）。我们对迄今为止发表的最大的高危 CMV 再激活患者队列进行了分析，结果表明，勒特洛韦预防可显著减少因 DNAemia 或 CMV 疾病而接受 CMV 活性抗病毒治疗的患者数量。
