背景:巨细胞病毒特异性T细胞介导的免疫(CMV-CMI)在异基因造血细胞移植(allo-HCT)中保护免受CMV感染,但迄今为止,该人群的CMV免疫没有经过验证的测量。
方法:在此前瞻性中,观察,试点研究,每月评估CMVT细胞反应,并在CMV血清阳性的allo-HCT受体发生移植物抗宿主病(GVHD)或CMV感染时,使用商业流式细胞术测定。CMVinSIGHTT细胞免疫面板(CMV-TCIP)。主要终点是CMV-TCIP首次阳性的时间,定义为产生干扰素-γ的CD4+或CD8+CMV特异性T细胞的百分比>0.2%。Letermovir从第+10天至≥100天开处方。
结果:登记了28名allo-HCT接受者。CD4+的CMV-TCIP首次阳性的中位时间较早(60天[四分位距,IQR33–148])比CD8T细胞(96天[IQR33–155])更长,单倍体和错配移植受体(77和96天,分别)比匹配的捐赠者(45天和33天,分别)。CD4+和CD8+CMV-CMI恢复在10/10(100%)和10/11(91%)患者中持续,分别,没有GVHD,而CD4+和/或CD8+CMV-CMI在4/6和2/6患者中丢失,分别,GVHD需要类固醇。作为低水平CMV再激活患者临床上显着CMV感染的预测因子,CMV-TCIP的敏感性和阴性预测值分别为90%和87.5%,分别,CD4+CMV-TCIP分别为66.7%和62.5%,分别,对于CD8+CMV-TCIP。
结论:HCT后CMV-CMI恢复的时间差异显著,单倍体和错配HCT后恢复较慢。CD4+CMV-CMI可以预防CS-CMVi,但GVHD的诊断和治疗可能会丧失免疫力。
BACKGROUND: Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population.
METHODS: In this prospective, observational, pilot
study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100.
RESULTS: Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP.
CONCLUSIONS: There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.