Frontiers in Pediatrics (Feb 2022)

Bayesian Modeling Immune Reconstitution Apply to CD34+ Selected Stem Cell Transplantation for Severe Combined Immunodeficiency

  • Jean-Sebastien Diana,
  • Jean-Sebastien Diana,
  • Naïm Bouazza,
  • Naïm Bouazza,
  • Chloe Couzin,
  • Martin Castelle,
  • Alessandra Magnani,
  • Elisa Magrin,
  • Jeremie Rosain,
  • Jean-Marc Treluyer,
  • Jean-Marc Treluyer,
  • Capucine Picard,
  • Capucine Picard,
  • Despina Moshous,
  • Despina Moshous,
  • Stéphane Blanche,
  • Stéphane Blanche,
  • Bénédicte Neven,
  • Bénédicte Neven,
  • Marina Cavazzana,
  • Marina Cavazzana

DOI
https://doi.org/10.3389/fped.2021.804912
Journal volume & issue
Vol. 9

Abstract

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Severe combined immunodeficiencies (SCIDs) correspond to the most severe form of primary immunodeficiency. Allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy are curative treatments, depending on the donor's availability and molecular diagnostics. A partially human leukocyte antigen (HLA)-compatible donor used has been developed for this specific HSCT indication in the absence of a matched donor. However, the CD34+ selected process induces prolonged post-transplant T-cell immunodeficiency. The aim here was to investigate a modeling approach to predict the time course and the extent of CD4+ T-cell immune reconstitution after CD34+ selected transplantation. We performed a Bayesian approach based on the age-related changes in thymic output and the cell proliferation/loss model. For that purpose, we defined specific individual covariates from the data collected from 10 years of clinical practice and then evaluated the model's predicted performances and accuracy. We have shown that this Bayesian modeling approach predicted the time course and extent of CD4+ T-cell immune reconstitution after SCID transplantation.

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