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

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.

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Authors

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 (2021). https://doi.org/10.1007/s10875-020-00961-w

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Keywords

  • Inborn errors of immunity
  • primary immunodeficiency diseases
  • viruses
  • immunotherapy