Impaired virus-specific T cell responses in patients with myeloproliferative neoplasms treated with ruxolitinib.
Elisa RumiEmanuela Sant'AntonioChiara CavalloniGiuditta ComolliVirginia Valeria FerrettiIrene CassanitiDaniela PietraChiara TrottiMichele CiboddoMilena FurioneDaniele VanniIlaria Carola CasettiCristina FavaronFausto BaldantiLuca ArcainiMario CazzolaPublished in: Hematological oncology (2020)
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.
Keyphrases
- epstein barr virus
- diffuse large b cell lymphoma
- peripheral blood
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- prognostic factors
- endothelial cells
- immune response
- single molecule
- induced apoptosis
- cell proliferation
- cell death
- machine learning
- cell free
- patient reported outcomes
- electronic health record
- nk cells
- signaling pathway
- circulating tumor cells
- single cell