Impaired virus-specific T cell responses in patients with myeloproliferative neoplasms treated with ruxolitinib.
Adult
Aged
Aged, 80 and over
CD4-Positive T-Lymphocytes
/ drug effects
CD8-Positive T-Lymphocytes
/ drug effects
Cytomegalovirus
/ drug effects
Cytomegalovirus Infections
/ drug therapy
Epstein-Barr Virus Infections
/ drug therapy
Female
Follow-Up Studies
Herpesvirus 4, Human
/ drug effects
Humans
Interferon-gamma
/ metabolism
Male
Middle Aged
Myeloproliferative Disorders
/ drug therapy
Nitriles
Prognosis
Pyrazoles
/ pharmacology
Pyrimidines
Survival Rate
Viral Load
Virus Activation
/ drug effects
JAK2
lymphocyte
myeloproliferative
ruxolitinib
virus
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
27
04
2020
revised:
21
06
2020
accepted:
22
06
2020
pubmed:
26
6
2020
medline:
3
11
2020
entrez:
26
6
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Nitriles
0
Pyrazoles
0
Pyrimidines
0
Interferon-gamma
82115-62-6
ruxolitinib
82S8X8XX8H
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
554-559Subventions
Organisme : MYNERVA
ID : 21267
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 5x1000
Organisme : Italian Ministry of Health for young researchers
ID : GR-2016-02361272
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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