Successful Haematopoietic Stem Cell Transplantation for LRBA Deficiency with Fludarabine, Treosulfan, and Thiotepa-Based Conditioning

J Clin Immunol. 2024 Sep 12;45(1):3. doi: 10.1007/s10875-024-01770-1.

Abstract

LRBA deficiency is an inborn error of immunity defined by autoimmunity, lymphoproliferation, recurrent infections, cytopenia, and inflammatory bowel disease. Despite recent advances in managing this disease with targeted biologic therapy, haematopoietic stem cell transplant (HSCT) remains the only cure. However, great variability exists between protocols used to transplant patients with LRBA deficiency. We describe a cohort of seven patients with LRBA deficiency who underwent HSCT using a myeloablative, reduced toxicity regime of fludarabine, treosulfan, and thiotepa at two transplantation centres from 2016 to 2019. Data were collected both retrospectively and prospectively, measuring time to engraftment, infectious complications, incidence of graft versus host disease, and post-transplantation chimerism. Six of seven patients survived transplantation, and four of six surviving patients achieving treatment-free survival. We thus recommend that HSCT with fludarabine, treosulfan, and thiotepa-based conditioning be considered in patients with LRBA deficiency.

Keywords: Graft vs host disease; Haematopoietic stem cell transplantation; Infectious complications; LRBA deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Busulfan* / analogs & derivatives
  • Busulfan* / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Infant
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / therapy
  • Male
  • Retrospective Studies
  • Thiotepa* / therapeutic use
  • Transplantation Conditioning* / methods
  • Treatment Outcome
  • Vidarabine* / analogs & derivatives
  • Vidarabine* / therapeutic use

Substances

  • Vidarabine
  • Busulfan
  • treosulfan
  • fludarabine
  • Thiotepa