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Assessment of the potential value of plasma Torque Teno virus DNA load monitoring to predict Cytomegalovirus DNAemia in patients with hematological malignancies treated with small molecule inhibitors: A proof-of-concept study
  • +11
  • David Navarro,
  • Carlos de la Asunción,
  • Estela Giménez,
  • Juan Hernández-Boluda,
  • María José Terol,
  • Eliseo Albert,
  • Javier López,
  • Valentín García-Gutiérrez,
  • Rafael Andreu,
  • María Dolores García Malo,
  • María Laura Fox,
  • María Remigia,
  • Paula Amat,
  • Carlos Solano
David Navarro
Hospital Clinico Universitario

Corresponding Author:david.navarro@uv.es

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Carlos de la Asunción
Hospital Clinico Universitario
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Estela Giménez
Hospital Clinico Universitario
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Juan Hernández-Boluda
Hospital Clinico Universitario
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María José Terol
Hospital Clinico Universitario
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Eliseo Albert
Hospital Clinico Universitario
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Javier López
Hospital Universitario Ramon y Cajal
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Valentín García-Gutiérrez
Hospital Universitario Ramon y Cajal
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Rafael Andreu
Hospital Universitari i Politecnic La Fe
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María Dolores García Malo
Hospital General Universitario Jose M Morales Meseguer
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María Laura Fox
Hospital Universitari Vall d'Hebron
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María Remigia
Hospital Clinico Universitario
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Paula Amat
Hospital Clinico Universitario
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Carlos Solano
Hospital Clinico Universitario
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Abstract

Background: It is unknown whether Torque Teno virus (TTV) DNA load monitoring could anticipate the development of infectious events in hematological patients undergoing treatment with small molecular targeting agents. We characterized the kinetics of plasma TTV DNA in patients treated with ibrutinib or ruxolitinib and assessed whether TTV DNA load monitoring could predict the occurrence of Cytomegalovirus (CMV) DNAemia or the magnitude of CMV-specific T-cell responses. Methods: Multicenter, retrospective, observational study, recruiting 20 patients treated with ibrutinib and 21 with ruxolitinib. Plasma TTV and CMV DNA loads were quantified by real-time PCR at baseline and days +15, +30, +45, +60, +75, +90, +120, +150, and +180 after treatment inception. Enumeration of CMV-specific IFN-γ-producing CD8 + and CD4 + T cells in whole blood was performed by flow cytometry. Results: Median TTV DNA load in ibrutinib-treated patients increased significantly ( P=0.025) from baseline (median, 5.76 log 10 copies/ml) to day +120 (median, 7.83 log 10 copies/ml). A moderate inverse correlation (Rho=-0.46; P<0.001) was found between TTV DNA load and absolute lymphocyte count (ALC). In ruxolitinib-treated patients, TTV DNA load quantified at baseline was not significantly different from that measured after treatment inception ( P ≥0.12). TTV DNA loads were not predictive of the subsequent occurrence of CMV DNAemia in either patient group. No correlation was observed between TTV DNA loads and CMV-specific IFN-γ-producing CD8 + and CD4 + T cell counts in either patient group. Conclusion: The data did not support the hypothesis that TTV DNA load monitoring in hematological patients treated with ibrutinib or ruxolitinib could be useful to predict either the occurrence of CMV DNAemia or the level of CMV-specific reconstitution.
19 Apr 2023Submitted to Journal of Medical Virology
03 May 2023Submission Checks Completed
03 May 2023Assigned to Editor
03 May 2023Review(s) Completed, Editorial Evaluation Pending
04 May 2023Reviewer(s) Assigned
30 May 2023Editorial Decision: Revise Major
19 Jun 20231st Revision Received
22 Jun 2023Submission Checks Completed
22 Jun 2023Assigned to Editor
22 Jun 2023Review(s) Completed, Editorial Evaluation Pending
22 Jun 2023Editorial Decision: Accept