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Reconstitution of cytomegalovirus-specific T-cell immunity following unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with posttransplant cyclophosphamide

Bone Marrow Transplantation volume 55, pages 1347–1356 (2020)Cite this article

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Abstract

Cytomegalovirus (CMV) DNAemia and CMV disease have been reported as more frequent in patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) than in those receiving HLA-matched allografts. This could be due to impaired CMV-specific T-cell reconstitution. Here, we conducted a multicenter observational study to assess CMV pp65 and IE-1-specific T cells kinetics in patients undergoing unmanipulated Haplo-HSCT with posttransplant cyclophosphamide (PT/Cy-haplo) and compared it with patients allografted with HLA-matched donors. Plasma CMV DNA load was monitored by real-time PCR and enumeration of CMV-specific IFN-γ-producing CD8+ and CD4+ T cells was performed by flow cytometry for intracellular cytokine staining at days +30, +60, +90, and +180 after transplantation. CMV DNAemia developed in 62 patients, occurring with comparable frequency in PT/Cy-haplo and MRD/MUD recipients (P = 0.14). There were no significant differences across groups in the number of patients either displaying detectable CMV-specific CD8+ and CD4+ T-cell responses or acquiring CMV-specific T-cell levels conferring protection against subsequent infection. CMV-specific T-cell counts were comparable between groups at most time points examined, irrespective of whether CMV DNAemia occurred or not prior to monitoring. Collectively the data suggest that PT/Cy-haplo recipients may reconstitute CMV-specific T-cell immunity to the same extent as patients undergoing HLA-matched allo-HSCT.

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Fig. 1: Detectable and protective CMV-specific T-cell responses in different transplantation platforms.

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Acknowledgements

EG holds a Juan Rodés research contract from the Carlos III Health Institute (Ref. JR18/00053). Eliseo Albert holds a Río Hortega research contract from the Carlos III Health Institute (Ref. CM18/00221).

Funding

This research was supported by grant 15/0090 from FIS (Fondo de Investigaciones Sanitarias), Ministerio de Sanidad y Consumo, Spain.

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Author notes

  1. These authors contributed equally: Dixie Huntley and Estela Giménez

Authors and Affiliations

  1. Microbiology Service, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain

    Dixie Huntley, Estela Giménez, Eliseo Albert & David Navarro

  2. Hematology Service, Hospital Regional Universitario, Málaga, Spain

    María Jesús Pascual & Beatriz Gago

  3. Hematology Service, Hospital Clínico Universitario, INCLIVA Research Institute, Valencia, Spain

    María José Remigia, Paula Amat, Juan Carlos Hernández-Boluda, José Luis Piñana, Ariadna Martínez & Carlos Solano

  4. Hematology Service, Hospital Clínico Universitario, Salamanca, Spain

    Lourdes Vázquez & Magdalena García

  5. Hematology Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Marta Hernández

  6. Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain

    Juan Carlos Hernández-Boluda & Carlos Solano

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

    Eva Mateo, Roberto Gozalbo-Rovira & David Navarro

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Correspondence to David Navarro.

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Huntley, D., Giménez, E., Pascual, M.J. et al. Reconstitution of cytomegalovirus-specific T-cell immunity following unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with posttransplant cyclophosphamide. Bone Marrow Transplant 55, 1347–1356 (2020). https://doi.org/10.1038/s41409-020-0865-x

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