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来特莫韦用于阿仑单抗去除T细胞的异基因造血干细胞移植后巨细胞病毒预防的疗效

Efficacy of Letermovir for Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant.

作者信息

Muhsen Ibrahim N, Shaver Kristen E, Wang Tao, Wu Mengfen, Lulla Premal, Ramos Carlos A, Kamble Rammurti T, Heslop Helen E, Carrum George, Hill LaQuisa C

机构信息

Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.

Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Texas.

出版信息

Transplant Cell Ther. 2024 Dec;30(12):1193.e1-1193.e8. doi: 10.1016/j.jtct.2024.09.009. Epub 2024 Sep 12.

Abstract

In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy or CMV disease) within 100 days post-transplant. Secondary outcomes included the cumulative incidence of acute GvHD (grade ≥ 2), the cumulative incidence of extensive chronic GvHD, and overall survival. A total of 84 alemtuzumab TCD URD allo-HSCT recipients were included in the analysis, 30 of whom received letermovir (letermovir group) and 54 who did not receive letermovir (control group). The median age was 59 years (range: 26-75 years) and 55.5 years (range: 20-73 years) in the letermovir and control group, respectively. Most recipients (66.7%) in both groups received unrelated matched allografts, and myeloid neoplasms were the most common indication for allo-HSCT. A significantly lower cumulative incidence of significant CMV infection within 100 days was seen in the letermovir group compared to the control group (10.0% [95% CI: 2.5-23.9%] versus 55.6% [95% CI: 41.2-67.8%], P < .0001). There was no statistically significant difference in the incidence of acute GvHD (grade ≥ 2) or overall survival between the 2 groups. However, lower rates of extensive chronic GvHD were noted in the letermovir group (10.5% [95% CI: 2.6-24.9%] versus. 36.5% [95% CI: 23.6-49.5%], P = .0126). These results demonstrate the efficacy of letermovir in decreasing the rates of clinically significant CMV infection in patients undergoing alemtuzumab T-cell depleted allo-HSCT.

摘要

使用阿仑单抗进行体内T细胞清除(TCD)可降低异基因造血干细胞移植(allo-HSCT)受者发生移植物抗宿主病(GvHD)的风险。然而,这种方法会增加allo-HSCT后感染的风险,包括巨细胞病毒(CMV)感染。来特莫韦已被批准用于allo-HSCT后的CMV预防。很少有研究调查来特莫韦在接受阿仑单抗治疗的患者中的疗效。这是一项单中心回顾性研究,描述了我们机构在接受阿仑单抗TCD的非血缘供者(URD)allo-HSCT受者中使用来特莫韦的经验。主要结局是移植后100天内严重CMV感染(定义为导致抢先抗病毒治疗的病毒血症或CMV疾病)的累积发生率。次要结局包括急性GvHD(≥2级)的累积发生率、广泛慢性GvHD的累积发生率和总生存期。共有84例接受阿仑单抗TCD的URD allo-HSCT受者纳入分析,其中30例接受来特莫韦治疗(来特莫韦组),54例未接受来特莫韦治疗(对照组)。来特莫韦组和对照组的中位年龄分别为59岁(范围:26-75岁)和55.5岁(范围:20-73岁)。两组中大多数受者(66.7%)接受了非血缘匹配的同种异体移植,骨髓肿瘤是allo-HSCT最常见的适应证。与对照组相比,来特莫韦组移植后100天内严重CMV感染的累积发生率显著降低(10.0% [95% CI:2.5-23.9%] 对55.6% [95% CI:41.2-67.8%],P <.0001)。两组之间急性GvHD(≥2级)的发生率或总生存期无统计学显著差异。然而,来特莫韦组广泛慢性GvHD的发生率较低(10.5% [95% CI:2.6-24.9%] 对36.5% [95% CI:23.6-49.5%],P =.0126)。这些结果证明了来特莫韦在降低接受阿仑单抗T细胞清除的allo-HSCT患者临床显著CMV感染率方面的疗效。

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