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Failure of Viral-Specific T Cells Administered in Pre-transplant Settings in Children with Inborn Errors of Immunity

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Abstract

Purpose

Use of adoptive immunotherapy with virus-specific T cells (VST) in patients with inborn errors of immunity prior to hematopoietic stem cell transplantation (HSCT) has been reported in few patients. We report our experience, reviewing all the cases previously reported.

Methods

We report four children with inborn errors of immunity who received VST infusion in a pre-HSCT setting in two reference centers in Spain and review all inborn errors of immunity cases previously reported.

Results

Taking into account our four cases, nine children have been reported to receive VST prior to HSCT to date: 3 severe combined immunodeficiency, 2 CTPS1 deficiency, 1 dyskeratosis congenital, 1 ORAI1 deficiency, 1 Rothmund-Thomson syndrome, and 1 combined immunodeficiency without confirmed genetic defect. In four patients, immunotherapy resulted in clinical improvement, allowing to proceed to HSCT. In these cases, the infusion was started closely to viral diagnosis [mean time 28 days (IQR; 17–52 days)], and the VST was followed shortly thereafter by HSCT [mean time 28 days (IQR; 10–99 days)]. Viremia was controlled after HSCT in two cases (performed 7 and 36 days after the infusion). Multiple infusions were required in many cases. Five out of nine patients died before receiving HSCT. These patients presented with a prolonged and uncontrolled infection before VST administration [mean time from viral diagnosis to VST infusion was 176 days (IQR; 54–1687)].

Conclusions

In patients with inborn errors of immunity, the efficacy of VST for treating disseminated viral infections in pre-transplant settings seems to have a limited efficacy. However, this therapy could be used in a pre-emptive setting before severe viral disease occurs or closely to HSCT.

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Acknowledgments

The authors acknowledge Kinga Sandor-Bajusz for the revision of the English language.

Author information

Author notes

  1. Laura Alonso and Ana Mendez-Echevarria have contributed equally, and they would like to share main authorship.

Authors and Affiliations

  1. HSCT Department, Hospital Vall d’Hebron, Barcelona, Spain

    Laura Alonso & Cristina Díaz de Heredia

  2. Paediatric Infectious Diseases Department, La Paz University Hospital, Madrid, Spain

    Ana Méndez-Echevarría

  3. Translational Research Network in Pediatric Infectious Diseases (RITIP), Paseo de la Castellana 261, 28046, Madrid, Spain

    Ana Méndez-Echevarría

  4. Immunogenetics and Histocompatibility Laboratory, Banc de Sang i Teixits, Barcelona, Spain

    Francesc Rudilla

  5. Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d’Hebron Research Institute, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

    Pere Soler-Palacin & Jacques Riviere

  6. Jeffrey Model Foundation Excellence Center, Barcelona, Spain

    Pere Soler-Palacin & Jacques Riviere

  7. Paediatric Hemato-Oncology Department, La Paz University Hospital, Madrid, Spain

    Yasmina Mozo, Luisa Sisinni, David Bueno & Antonio Pérez-Martínez

  8. Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain

    Yasmina Mozo, Luisa Sisinni, David Bueno & Antonio Pérez-Martínez

  9. Hematology Department, La Paz University Hospital, Madrid, Spain

    Raquel de Paz

  10. Immunology Department, La Paz University Hospital, Madrid, Spain

    Elena Sánchez-Zapardiel, Rebeca Rodriguez-Pena & Eduardo López-Granados

  11. IdiPAZ Institute for Health Research, Madrid, Spain

    Elena Sánchez-Zapardiel, Rebeca Rodriguez-Pena & Eduardo López-Granados

  12. Cellular Therapy Unit, Cord Blood Bank, Centre Frederic Duran i Jordà, Barcelona, Spain

    Sergi Querol

  13. Laboratory of Immunology, Department of Pathology, Hospital del Mar, Barcelona, Spain

    Ramón Gimeno

Authors
  1. Laura Alonso
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  2. Ana Méndez-Echevarría
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  3. Francesc Rudilla
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  4. Yasmina Mozo
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  5. Pere Soler-Palacin
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  6. Luisa Sisinni
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  7. David Bueno
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  8. Jacques Riviere
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  9. Raquel de Paz
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  10. Elena Sánchez-Zapardiel
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  11. Sergi Querol
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  12. Rebeca Rodriguez-Pena
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  13. Eduardo López-Granados
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  14. Ramón Gimeno
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  15. Cristina Díaz de Heredia
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  16. Antonio Pérez-Martínez
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Contributions

A. Mendez-Echevarria/L. Alonso/A. Perez-Martinez: They designed the research and analyzed data. They wrote the first draft; F.Rudilla, R. de Paz, E. Sanchez-Zapardiel, S. Querol, and E. Lopez-Granados: They wrote methods regarding VST production and administration in both hospitals and reviewed the literature regarding VST production and donor selection in primary immunodeficiencies; R. Gimeno wrote methods regarding assessing immune reactivity against CMV antigen using interferon-enzyme linked immunospot assay in patient 3. He is the author of Supplementary File 3; L. Sisinni, D. Bueno, Y. Mozo, and R. Rodriguez-Pena: collected clinical data regarding HSCT, viral treatments, clinical outcome in Hospital La Paz; P.Soler-Palacin and J.Riviere: collected clinical data regarding HSCT, viral treatments, and clinical outcome in Hospital Vall d’Hebron; all the authors corrected and approved the final manuscript.

Corresponding author

Correspondence to Ana Méndez-Echevarría.

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Alonso, L., Méndez-Echevarría, A., Rudilla, F. et al. Failure of Viral-Specific T Cells Administered in Pre-transplant Settings in Children with Inborn Errors of Immunity. J Clin Immunol 41, 748–755 (2021). https://doi.org/10.1007/s10875-020-00961-w

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  • DOI: https://doi.org/10.1007/s10875-020-00961-w

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