Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct;38(4):554-559.
doi: 10.1002/hon.2769. Epub 2020 Jul 22.

Impaired virus-specific T cell responses in patients with myeloproliferative neoplasms treated with ruxolitinib

Elisa Rumi  1   2 , Emanuela Sant'Antonio  3 , Chiara Cavalloni  2 , Giuditta Comolli  4   5 , Virginia Valeria Ferretti  1 , Irene Cassaniti  4 , Daniela Pietra  2 , Chiara Trotti  1 , Michele Ciboddo  1 , Milena Furione  4 , Daniele Vanni  1 , Ilaria Carola Casetti  1 , Cristina Favaron  1 , Fausto Baldanti  4   6 , Luca Arcaini  1   2 , Mario Cazzola  1   2
Affiliations

Impaired virus-specific T cell responses in patients with myeloproliferative neoplasms treated with ruxolitinib

Elisa Rumi et al. Hematol Oncol. 2020 Oct.

Abstract

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.

Keywords: JAK2; lymphocyte; myeloproliferative; ruxolitinib; virus.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

REFERENCES

    1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.
    1. Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129(6):667-679.
    1. Villarino AV, Kanno Y, O'Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol. 2017;18(4):374-384.
    1. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798.
    1. Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of INCB018424, an oral, selective JAK1/JAK2 inhibitor, in patients with advanced polycythemia vera (PV) and essential thrombocythemia (ET) refractory to hydroxyurea. Blood. 2009;114(22):132.

MeSH terms