학술논문
Torque Teno Virus plasma DNA load: a novel prognostic biomarker in CAR-T therapy.
Document Type
Academic Journal
Author
Benzaquén A; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Giménez E; Microbiology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Iacoboni G; Haematology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.; Guerreiro M; Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Hernani R; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Albert E; Microbiology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Carpio C; Haematology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; Balaguer A; Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Pérez A; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; S de la Asunción C; Microbiology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Sánchez-Salinas MA; Haematology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; Chorão P; Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Piñana JL; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Beas F; Haematology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; Montoro J; Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Hernández-Boluda JC; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Department of Medicine, University of Valencia, Valencia, Spain.; Facal A; Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Ferrer B; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Villalba M; Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Amat P; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Department of Medicine, University of Valencia, Valencia, Spain.; Goméz MD; Microbiology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Campos D; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Terol MJ; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Department of Medicine, University of Valencia, Valencia, Spain.; Sanz J; Haematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.; Department of Medicine, University of Valencia, Valencia, Spain.; Barba P; Haematology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain. pebarba@vhebron.net.; Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain. pebarba@vhebron.net.; Navarro D; Microbiology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Department of Microbiology, University of Valencia, Valencia, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Solano C; Haematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain.; Department of Medicine, University of Valencia, Valencia, Spain.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8702459 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5365 (Electronic) Linking ISSN: 02683369 NLM ISO Abbreviation: Bone Marrow Transplant Subsets: MEDLINE
Subject
Language
English
Abstract
Torque Teno Virus (TTV) is a single-stranded circular DNA virus which has been identified as a surrogate marker of immune competence in transplantation. In this study we investigated the dynamics of plasma TTV DNAemia in 79 adult patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory large B-cell lymphoma, also evaluating the impact of TTV on immunotoxicities, response and survival outcomes. After lymphodepleting therapy, TTV DNA load was found to decrease slightly until reaching nadir around day 10, after which it increased steadily until reaching maximum load around day 90. TTV DNA load < 4.05 log10 copies/ml at immune effector cell-associated neurotoxicity syndrome (ICANS) onset identified patients at risk of progressing to severe forms of ICANS (OR 16.68, P = 0.048). Finally, patients who experienced falling or stable TTV DNA load between lymphodepletion and CAR-T infusion had better progression-free survival than those with ascending TTV DNA load (HR 0.31, P = 0.006). These findings suggest that TTV monitoring could serve as a surrogate marker of immune competence, enabling predictions of CAR-T efficacy and toxicity. This could pave the way for the development of TTV-guided therapeutic strategies that modulate clinical patient management based on plasma TTV load, similar to suggested strategies in solid organ transplant recipients.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)