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异基因造血细胞移植后第一年难治性巨细胞病毒感染的结果。

Outcomes of Refractory Cytomegalovirus Infection in the First Year after Allogeneic Hematopoietic Cell Transplantation.

机构信息

Infectious Disease Service, Memorial Sloan Kettering Cancer Center, New York, New York.

Infectious Disease Service, Memorial Sloan Kettering Cancer Center, New York, New York; Laboratory of Translational Oncology, Medical School, University of Crete, Greece.

出版信息

Transplant Cell Ther. 2022 Jul;28(7):403.e1-403.e7. doi: 10.1016/j.jtct.2022.04.016. Epub 2022 Apr 25.

Abstract

Outcomes of refractory (Rf) cytomegalovirus (CMV) infection (CMVi) after hematopoietic cell transplantation (HCT) are poor owing to limited treatment options and treatment related toxicities. Maribavir, an orally bioavailable CMV antiviral, was recently approved for treatment of Rf-CMVi. Real-world studies quantifying the burden of Rf-CMVi prior to maribavir provide a benchmark for evaluating the net value of novel treatments. Here we report the incidence, clinical outcomes, and healthcare resource utilization (HRU) associated with Rf-CMVi in the first year post-HCT in a cohort of CMV-seropositive HCT recipients (R+) who underwent HCT between January 1, 2014, and December 31, 2017, at Memorial Sloan Kettering Cancer Center and were managed exclusively by preemptive therapy. CMVi was defined as CMV viremia treated preemptively. Rf-CMVi was defined as a <1 log decrease and CMV viral load >1000 U/mL after ≥14 days of appropriately dosed therapy. Welldays were defined as alive days not hospitalized and off CMV antivirals by 1 year post-HCT. The impact of Rf-CMVi on mortality and HRU was examined in multivariable models. Of the 286 R+ patients, 145 (50.7%) developed CMVi (99 no Rf-CMVi and 46 Rf-CMVi). Compared with the no Rf-CMVi group, the Rf-CMVi group had higher rates of CMV EOD (23.9% versus 10.1%; P = .030), CMV-related mortality (9.5% versus .0%; P = .002), and all-cause mortality (33.3% versus 15.6%; adjusted P = .049). Rf-CMVi was an independent predictor for readmission (adjusted odds ratio [aOR], 3.24; 95% confidence interval [CI], 2.19 to 4.87; P < .0001); CMV-related readmission (aOR, 9.48; 95% CI, 5.83 to 15.80; P < .0001), and decreased well days (adjusted arithmetic mean ratio, .72; 95% CI, .58 to .89; P = .001) in the first year post-HCT. Rf-CMVi is associated with increased mortality and increased HRU at 1 year after HCT. Improved therapies for Rf-CMVi have the potential of improving HCT outcomes and reducing HRU.

摘要

造血细胞移植(HCT)后难治性(Rf)巨细胞病毒(CMV)感染(CMVi)的结局较差,这是由于治疗选择有限和治疗相关毒性所致。马拉韦罗,一种口服生物可利用的 CMV 抗病毒药物,最近被批准用于治疗 Rf-CMVi。在接受 HCT 的 CMV 血清阳性 HCT 受者(R+)中,在接受 HCT 前进行的评估 Rf-CMVi 负担的真实世界研究为评估新型治疗方法的净价值提供了基准。在此,我们报告了在 Memorial Sloan Kettering 癌症中心接受 HCT 的 CMV 血清阳性 HCT 受者(R+)中,HCT 后第一年中与 Rf-CMVi 相关的发病率、临床结局和医疗资源利用(HRU),这些患者在 2014 年 1 月 1 日至 2017 年 12 月 31 日期间接受了 HCT,并且仅通过抢先治疗进行管理。CMVi 定义为预防性治疗的 CMV 病毒血症。Rf-CMVi 定义为在接受≥14 天适当剂量治疗后,CMV 病毒载量下降<1 log 且>1000 U/mL。Welldays 定义为在 HCT 后 1 年内未住院且未接受 CMV 抗病毒药物治疗的存活天数。在多变量模型中检查了 Rf-CMVi 对死亡率和 HRU 的影响。在 286 名 R+患者中,有 145 名(99 名无 Rf-CMVi 和 46 名 Rf-CMVi)发生了 CMVi。与无 Rf-CMVi 组相比,Rf-CMVi 组 CMV EOD 的发生率更高(23.9%比 10.1%;P=0.030)、CMV 相关死亡率(9.5%比 0.0%;P=0.002)和全因死亡率(33.3%比 15.6%;调整后 P=0.049)。Rf-CMVi 是再入院的独立预测因素(调整后优势比[aOR],3.24;95%置信区间[CI],2.19 至 4.87;P<0.0001);CMV 相关再入院(aOR,9.48;95%CI,5.83 至 15.80;P<0.0001)和 HCT 后第一年 Welldays 减少(调整后算术平均值比,0.72;95%CI,0.58 至 0.89;P=0.001)。Rf-CMVi 与 HCT 后 1 年死亡率增加和 HRU 增加相关。改善 Rf-CMVi 的治疗方法有可能改善 HCT 结局并减少 HRU。

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