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Allogeneic hematopoietic cell transplantation for partial RAG deficiency in children and adults: excellent outcomes with a reduced intensity, posttransplantation cyclophosphamide-based approach - PubM

4 hours ago
  • #hematopoietic cell transplantation
  • #partial RAG deficiency
  • #immune dysregulation
  • Allogeneic hematopoietic cell transplantation (HCT) is effective for partial RAG deficiency (pRD) in children and adults.
  • A reduced-intensity conditioning (RIC) approach with post-transplantation cyclophosphamide (PTCy) shows excellent outcomes.
  • Overall survival rates were high: 92% at 1 year and 83% at 2 years for the entire cohort.
  • RIC recipients (n=12) had 100% and 90% survival at 1 and 2 years, respectively.
  • Clinical manifestations reversed with immune reconstitution, minimal de novo autoimmunity, and low GVHD incidence.
  • Va7.2+ T cells increased rapidly post-HCT, while mucosa-associated invariant T cell reconstitution lagged.
  • Dysreactive B cells and autoantibodies decreased post-HCT.
  • Anti-type I interferon antibodies decreased slowly but neutralizing activity was reduced.
  • Outcomes were not affected by donor carrier status or HLA-matching.
  • Bronchiectasis exacerbations required rehospitalization in patients with irreversible lung disease pre-HCT.