Déficits congénitaux de l'immunité cellulaire et thérapie cellulaire : l'apport de la thérapie cellulaire dans la prévention des complications survenant au décours des allogreffes de cellules souches hématopoïétiques

Abstract : Allogeneic hematopoietk stem cell transplantation (HSCT) is the only way to cure severe Primary Immune Deficiencies (PID). However, HSCT is, sometimes complicated by infections or Graft vers us Host disease (GVHD) which can lead to patient death. In this work we illustrate how, for three PIDs, Hyper IgM syndrome (HIGM), Wiskott Aldrich Syndrome (WAS) and DiGeorge syndrome (cDGS), expert knowledge of the disease and its complications together with optimal management of the allogeneic HSCT procedure both increase the chances for a successful outcome. Analysing post-HSCT infections, we explain how B-cell depletion is very effective in preventing EBV -related lymphoproliferative syndromes. We also report the successful treatment of a pre-transplant Cryptosporidium parvum infection in two children with X-linked HIGM by an allogeneic HSCT that led to cure of the CD40L deficiency. Nevertheless, such an effective result seems to be favored by the absence of severe hepatic impairment at the time of transplant. We then study how to prevent GVHD by graft manipulations. We report CD34-positive selection limits in a patient with W AS and we also present different alloreactive depletion methods to prevent GVHD while preserving graft anti-infectious capacity. Finally, in the specifie case of cDGS, we report on the effectiveness of unmanipulated peripheral blood mononuclear cell infusion to avoid a conditioning regimen and to simplify allogeneic transplantation procedure.
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Danièle Bensoussan-Lejzerowicz. Déficits congénitaux de l'immunité cellulaire et thérapie cellulaire : l'apport de la thérapie cellulaire dans la prévention des complications survenant au décours des allogreffes de cellules souches hématopoïétiques. Autre. Université Henri Poincaré - Nancy 1, 2007. Français. ⟨NNT : 2007NAN11305⟩. ⟨tel-01747445⟩

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