The GLIO-CMV-01 study is a prospective observational study, conducted at the Department of Radiation Oncology of the Universitätsklinikum Erlangen in Germany. It is a registered clinical trial (ClinicalTrials ID: NCT02600065). The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Friedrich-Alexander Universität Erlangen-Nürnberg (protocol code: 265_14B; date of approval: 18 September 2014). Informed consent was obtained from all subjects involved in the study.
Patients enrolled in the trial either suffered from high-grade gliomas (WHO grades III-IV) or brain metastases. The patients received local RT of the brain or whole-brain RT. The duration of local RT was 42 to 45 days and the duration of whole-brain RT was 14 to 28 days. Blood samples were taken before, in the middle of, and at the end of RT. Peripheral blood was tested for anti-CMV IgM, anti-CMV IgG, and CMV DNA. The testing was performed by the Institute of Virology of the Universitätsklinikum Erlangen immediately after the blood withdrawal. Viremia was defined as ≥250 copies/mL by real-time PCR. CMV-associated encephalopathy was considered proven if neurological decline occurred together with viremia. MRI scans were performed to exclude other explanations for the neurological decline. In the case of CMV-associated encephalopathy, patients were treated with ganciclovir or valganciclovir [2 (link),3 (link)].
Simultaneously with the CMV analyses, whole blood immunophenotyping was performed as described in previously published protocols. Thereby, a detailed peripheral immune status of the patients was obtained throughout the study, covering nine main immune cell types and numerous subtypes and their respective activation status [5 (link),6 (link),7 (link)]. In the here presented analysis, we additionally determined TEMRA cells and their subsets by multicolor flow cytometry in patients enrolled in the GLIO-CMV-01 study as well as in a group of healthy donors without tumor disease or radiation therapy. The inclusion of healthy donors was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Friedrich-Alexander Universität Erlangen-Nürnberg (protocol code: 21-15-B; date of approval: 9 November 2022). Informed consent was obtained from all subjects involved in the study. All flow cytometric analyses were performed from whole blood without previous isolation of mononuclear cells.
Patients enrolled in the trial either suffered from high-grade gliomas (WHO grades III-IV) or brain metastases. The patients received local RT of the brain or whole-brain RT. The duration of local RT was 42 to 45 days and the duration of whole-brain RT was 14 to 28 days. Blood samples were taken before, in the middle of, and at the end of RT. Peripheral blood was tested for anti-CMV IgM, anti-CMV IgG, and CMV DNA. The testing was performed by the Institute of Virology of the Universitätsklinikum Erlangen immediately after the blood withdrawal. Viremia was defined as ≥250 copies/mL by real-time PCR. CMV-associated encephalopathy was considered proven if neurological decline occurred together with viremia. MRI scans were performed to exclude other explanations for the neurological decline. In the case of CMV-associated encephalopathy, patients were treated with ganciclovir or valganciclovir [2 (link),3 (link)].
Simultaneously with the CMV analyses, whole blood immunophenotyping was performed as described in previously published protocols. Thereby, a detailed peripheral immune status of the patients was obtained throughout the study, covering nine main immune cell types and numerous subtypes and their respective activation status [5 (link),6 (link),7 (link)]. In the here presented analysis, we additionally determined TEMRA cells and their subsets by multicolor flow cytometry in patients enrolled in the GLIO-CMV-01 study as well as in a group of healthy donors without tumor disease or radiation therapy. The inclusion of healthy donors was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Friedrich-Alexander Universität Erlangen-Nürnberg (protocol code: 21-15-B; date of approval: 9 November 2022). Informed consent was obtained from all subjects involved in the study. All flow cytometric analyses were performed from whole blood without previous isolation of mononuclear cells.
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