Features of cytomegalovirus DNAemia and virus-specific T-cell responses in allogeneic hematopoietic stem-cell transplant recipients during prophylaxis with letermovir.

Fecha de publicación: 07/02/2023 Fecha Ahead of Print: 07/02/2023

Autores de IIS La Fe

Manuel Nuno Direito De Morais Guerreiro

Autor
Cristóbal Eduardo Aguilar Gallardo

Autor
José Luis Piñana Sánchez

Autor
Juan Bautista Montoro Gómez

Autor

Participantes ajenos a IIS La Fe

Gimenez, Estela
Torres, Ignacio
Albert, Eliseo
Hernandez-Boluda, Juan Carlos
Hernani, Rafael
Perez, Ariadna
Amat, Paula
Solano, Carlos
Navarro, David

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

Abstract

BACKGROUND: There is scarce information on the natural kinetics of cytomegalovirus (CMV) DNAemia and dynamics of CMV-specific T-cell reconstitution in allogeneic hematopoietic transplant recipients (allo-HSCT) undergoing letermovir (LMV) prophylaxis. METHODS: Twelve adult CMV-seropositive high-risk recipients (median age, 53 years; 9 males/3 females) undergoing LMV prophylaxis and 13 non-LMV allo-HSCT controls (median age, 58 years; 7 males/6 females) were included. CMV DNAemia in plasma was monitored by real-time polymerase chain reaction. Preemptive antiviral therapy (PET) was administered upon detection of =1500 IU/ml. CMV-specific interferon-gamma (IFN-?)-producing CD8(+) and CD4(+) T cells were enumerated by flow cytometry around days +30, +60, and +90 after allo-HSCT. Ex vivo experiments assessing of the potential effect of LMV on CMV-specific T-cell expansion in a single CMV-seropositive donor were also conducted. RESULTS: Five LMV patients (41.6%) developed CMV DNAemia that cleared spontaneously. Four patients (33.3%) developed CMV DNAemia after LMV cessation, of which two required PET. Nine non-LMV patients (69.2%) developed CMV DNAemia (five required PET). The percentage of LMV and non-LMV patients exhibiting detectable CMV-specific T-cell responses was comparable (7/10 vs. 10/13; p = .71). Nevertheless, median CMV-specific CD4(+) and CD8(+) T-cell counts were lower in LMV patients by days +60 (p = .006 and .02, respectively) and +90 (p = .08 and .02). Ex vivo, CMV-specific CD8(+) T cells expanded to the same level either in the presence (19.8%) or in the absence of LMV (20.6%). CONCLUSIONS: In our series, episodes of CMV DNAemia in LMV patients cleared spontaneously. A diminished degree of CMV-specific T-cell reconstitution in LMV patients compared to non-LMV patients was observed.

Datos de la publicación

ISSN/ISSNe:: 1398-2273, 1399-3062
Tipo:: Article
Páginas:: 14021-14021
DOI:: 10.1111/tid.14021
Factor de Impacto:: 0,536 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Métricas

Filiaciones

Gimenez, Estela:: Microbiology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain

Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
Guerreiro, Manuel:: Hematology Service, Hospital Universitario y Politécnico "La Fe", Valencia, Spain
Torres, Ignacio:: Microbiology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain
Aguilar, Cristobal:: Hematology Service, Hospital Universitario y Politécnico "La Fe", Valencia, Spain
Albert, Eliseo:: Microbiology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain
Hernandez-Boluda, Juan Carlos:: Hematology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain

Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain
Hernani, Rafael:: Hematology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain
Perez, Ariadna:: Hematology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain
Amat, Paula:: Hematology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain

Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain
Piñana JL:: Hematology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain
Montoro, Juan:: Hematology Service, Hospital Universitario y Politécnico "La Fe", Valencia, Spain
Solano, Carlos:: Hematology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain

Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain
Navarro, David:: Microbiology Service, Hospital Clínico Universitario, INCLIVA Health Research Institute, Valencia, Spain

Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain

Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain