Microbiology Service, INCLIVA Research Institute, Hospital Clínico Universitario, Valencia, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
J Med Virol. 2023 Jul;95(7):e28933. doi: 10.1002/jmv.28933.
It is unknown whether Torque Teno virus (TTV) DNA load monitoring could anticipate the development of infectious events in hematological patients undergoing treatment with small molecular targeting agents. We characterized the kinetics of plasma TTV DNA in patients treated with ibrutinib or ruxolitinib and assessed whether TTV DNA load monitoring could predict the occurrence of Cytomegalovirus (CMV) DNAemia or the magnitude of CMV-specific T-cell responses. Multicenter, retrospective, observational study, recruiting 20 patients treated with ibrutinib and 21 with ruxolitinib. Plasma TTV and CMV DNA loads were quantified by real-time PCR at baseline and days +15, +30, +45, +60, +75, +90, +120, +150, and +180 after treatment inception. Enumeration of CMV-specific interferon-γ (IFN-γ)-producing CD8 and CD4 T-cells in whole blood was performed by flow cytometry. Median TTV DNA load in ibrutinib-treated patients increased significantly (p = 0.025) from baseline (median: 5.76 log copies/mL) to day +120 (median: 7.83 log copies/mL). A moderate inverse correlation (Rho = -0.46; p < 0.001) was found between TTV DNA load and absolute lymphocyte count. In ruxolitinib-treated patients, TTV DNA load quantified at baseline was not significantly different from that measured after treatment inception (p ≥ 0.12). TTV DNA load was not predictive of the subsequent occurrence of CMV DNAemia in either patient group. No correlation was observed between TTV DNA loads and CMV-specific IFN-γ-producing CD8 and CD4 T-cell counts in either patient group. The data did not support the hypothesis that TTV DNA load monitoring in hematological patients treated with ibrutinib or ruxolitinib could be useful to predict either the occurrence of CMV DNAemia or the level of CMV-specific T-cell reconstitution; nevertheless, due to the small sample size, further studies involving larger cohorts are warranted to elucidate this issue.
目前尚不清楚 Torque Teno 病毒（TTV）DNA 载量监测是否可以预测接受小分子靶向药物治疗的血液病患者发生感染事件。我们描述了接受伊布替尼或芦可替尼治疗的患者血浆 TTV DNA 的动力学，并评估了 TTV DNA 载量监测是否可以预测巨细胞病毒（CMV）DNA 血症的发生或 CMV 特异性 T 细胞反应的程度。这是一项多中心、回顾性、观察性研究，共纳入 20 例接受伊布替尼治疗和 21 例接受芦可替尼治疗的患者。在治疗开始时及治疗后第 15、30、45、60、75、90、120、150 和 180 天，通过实时 PCR 定量检测血浆 TTV 和 CMV DNA 载量。通过流式细胞术检测全血中 CMV 特异性干扰素-γ（IFN-γ）产生的 CD8 和 CD4 T 细胞的计数。伊布替尼治疗患者的 TTV DNA 载量从基线（中位数：5.76 log 拷贝/ml）显著增加（p=0.025）至治疗后第 120 天（中位数：7.83 log 拷贝/ml）。在伊布替尼治疗患者中，TTV DNA 载量与绝对淋巴细胞计数呈中度负相关（Rho=-0.46；p<0.001）。在芦可替尼治疗患者中，基线时和治疗开始后测量的 TTV DNA 载量无显著差异（p≥0.12）。在两组患者中，TTV DNA 载量均不能预测随后发生 CMV DNA 血症。在两组患者中，TTV DNA 载量与 CMV 特异性 IFN-γ产生的 CD8 和 CD4 T 细胞计数均无相关性。数据不支持在接受伊布替尼或芦可替尼治疗的血液病患者中监测 TTV DNA 载量可用于预测 CMV DNA 血症的发生或 CMV 特异性 T 细胞重建水平的假设；然而，由于样本量小，需要进一步的研究来阐明这一问题。
