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Purpose <p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is successful in pediatric patients with inborn errors of immunity (IEI), but its use in adults is complicated by pre-existing organ damage and increased risk of treatment-related mortality. <i>Ex vivo</i> graft engineering using αβTCR/CD19 depletion has shown promising safety profiles in pediatric IEI, yet evidence in adults is limited. We assessed the feasibility and outcomes of αβTCR/CD19-depleted allo-HSCT in adults with IEI, focusing on engraftment, immune reconstitution, and clinical outcomes.</p> Methods <p>We included 9 adults with IEI and 1 with VEXAS (age 21–51). IEIs included CTLA4HI, APDS, DOCK8, ALPS, DADA2, CVID2, and HA20, with Immune Deficiency and Dysregulation Activity (IDDA) scores of 17–92. αβTCR/CD19-depleted allografts from related, unrelated or haplo-identical donors were used after antithymocyte globulin (ATG) and myeloablative conditioning (thiotepa, melphalan, and fludarabine). Post-transplant immunoprophylaxis included mycophenolate mofetil; 4/10 patients received additional transplant-associated immunosuppression.</p> Results <p>All patients achieved primary engraftment. One patient with secondary rejection successfully underwent a second allo-HSCT. 5 patients developed grade 2–4 acute GvHD; no chronic GvHD was observed. One patient with GvHD died from COVID-19. All remaining 9 patients were successfully tapered off immunosuppression and showed improved IDDA scores. At 6 months NK, γδT, B and CD8 + T cells normalized; CD4 + numbers reached 149 cells/µl at 1 year. Most patients were successfully vaccinated and could stop immunoglobulin substitution.</p> Conclusion <p>In conclusion, <i>ex vivo</i> graft engineering using αβTCR/CD19 depletion was feasible in adults with IEI. Clinical outcomes are encouraging, but need to be confirmed in larger studies.</p>

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αβT/CD19-depleted Allogeneic Stem Cell Transplantation in Adults with Inborn Errors of Immunity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月3日

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  • Janneke J. H. de Winter,
  • Birtan M. Ibrahimov,
  • Frances A. Verheij,
  • Iris D. Brinkman,
  • Anniek H. G. Stuut,
  • Pleun Schonewille,
  • Marloes W. Heijstek,
  • Anna van Rhenen,
  • Lotte E. van der Wagen,
  • Laura G. M. Daenen,
  • Anke Janssen,
  • Tim J. A. Hutten,
  • Jürgen Kuball,
  • Helen L. Leavis,
  • Moniek A. de Witte

摘要

Purpose

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is successful in pediatric patients with inborn errors of immunity (IEI), but its use in adults is complicated by pre-existing organ damage and increased risk of treatment-related mortality. Ex vivo graft engineering using αβTCR/CD19 depletion has shown promising safety profiles in pediatric IEI, yet evidence in adults is limited. We assessed the feasibility and outcomes of αβTCR/CD19-depleted allo-HSCT in adults with IEI, focusing on engraftment, immune reconstitution, and clinical outcomes.

Methods

We included 9 adults with IEI and 1 with VEXAS (age 21–51). IEIs included CTLA4HI, APDS, DOCK8, ALPS, DADA2, CVID2, and HA20, with Immune Deficiency and Dysregulation Activity (IDDA) scores of 17–92. αβTCR/CD19-depleted allografts from related, unrelated or haplo-identical donors were used after antithymocyte globulin (ATG) and myeloablative conditioning (thiotepa, melphalan, and fludarabine). Post-transplant immunoprophylaxis included mycophenolate mofetil; 4/10 patients received additional transplant-associated immunosuppression.

Results

All patients achieved primary engraftment. One patient with secondary rejection successfully underwent a second allo-HSCT. 5 patients developed grade 2–4 acute GvHD; no chronic GvHD was observed. One patient with GvHD died from COVID-19. All remaining 9 patients were successfully tapered off immunosuppression and showed improved IDDA scores. At 6 months NK, γδT, B and CD8 + T cells normalized; CD4 + numbers reached 149 cells/µl at 1 year. Most patients were successfully vaccinated and could stop immunoglobulin substitution.

Conclusion

In conclusion, ex vivo graft engineering using αβTCR/CD19 depletion was feasible in adults with IEI. Clinical outcomes are encouraging, but need to be confirmed in larger studies.