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

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

doi:10.3389/fped.2021.804912

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

Front Pediatr. 2022 Feb 15:9:804912. doi: 10.3389/fped.2021.804912. eCollection 2021.

Authors

Jean-Sebastien Diana^{1

2}, Naïm Bouazza^{2

3}, Chloe Couzin¹, Martin Castelle⁴, Alessandra Magnani¹, Elisa Magrin¹, Jeremie Rosain⁵, Jean-Marc Treluyer^{2

3}, Capucine Picard^{2

5}, Despina Moshous^{2

4}, Stéphane Blanche^{2

4}, Bénédicte Neven^{2

4}, Marina Cavazzana^{1

2}

Affiliations

¹ Biotherapy Department, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
² Université de Paris, Paris, France.
³ Clinical Research Unit, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁴ Pediatric Hematology-Immunology-Rheumatology Unit, Hôpital Necker Enfants Malades Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ Laboratory of Human Genetics of Infectious Diseases, Hôpital Necker Enfants Malades Assistance Publique-Hôpitaux de Paris, Paris, France.

Abstract

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.

Keywords: Bayesian prediction algorithm; CD34+ selection; hematopoietic stem cell transplantation; immune reconstitution; severe combined immunodeficiency (SCID).