Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Hematol Oncol. 2020 Oct;38(4):554-559. doi: 10.1002/hon.2769. Epub 2020 Jul 22.
Ruxolitinib is effective in myeloproliferative neoplasms (MPN) but can cause reactivation of silent infections. We aimed at evaluating viral load and T-cell responses to human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in a cohort of 25 MPN patients treated with ruxolitinib. EBV-DNA and HCMV-DNA were quantified monthly using real-time polimerase chain reaction (PCR) on peripheral blood samples, and T-cell subsets were analyzed by flowcytometry. HCMV and EBV-directed T-cell responses were evaluated using the IFN-γ ELISPOT assay. Most patients had CD4+ and/or CD8+ T-cells below the normal range; these reductions were related to the duration of ruxolitinib treatment. In fact, reduced T-lymphocytes' subsets were found in 93% of patients treated for ≥5 years and in 45% of those treated for <5 years (P = .021). The former also had lower median numbers of CD4+ and CD8+ cells. Subclinical reactivation of EBV and HCMV occurred in 76% and 8% of patients. We observed a trend to an inverse relationship between EBV and CMV-specific CD4+ and CD8+ T-cell responses and viral load, and a trend to an inverse correlation with ruxolitinib dose. Therefore, our data suggest that the ruxolitinib treatment may interfere with immunosurveillance against EBV and HCMV.
芦可替尼在骨髓增殖性肿瘤（MPN）中有效，但可能会引起潜伏感染的再激活。我们旨在评估 25 例接受芦可替尼治疗的 MPN 患者的病毒载量和针对人巨细胞病毒（HCMV）和 EBV 的 T 细胞反应。通过外周血样本实时聚合酶链反应（PCR）每月定量 EBV-DNA 和 HCMV-DNA，并通过流式细胞术分析 T 细胞亚群。通过 IFN-γ ELISPOT 测定评估 HCMV 和 EBV 定向 T 细胞反应。大多数患者的 CD4+和/或 CD8+T 细胞低于正常范围；这些减少与芦可替尼治疗的持续时间有关。事实上，在接受治疗≥5 年的患者中，93%发现 T 淋巴细胞亚群减少，而在接受治疗<5 年的患者中，45%发现 T 淋巴细胞亚群减少（P=0.021）。前者的 CD4+和 CD8+细胞中位数也较低。76%和 8%的患者发生 EBV 和 HCMV 的亚临床再激活。我们观察到 EBV 和 CMV 特异性 CD4+和 CD8+T 细胞反应与病毒载量呈负相关趋势，与芦可替尼剂量呈负相关趋势。因此，我们的数据表明，芦可替尼治疗可能会干扰针对 EBV 和 HCMV 的免疫监视。
