Journal of clinical immunology · 2026
αβT/CD19-depleted Allogeneic Stem Cell Transplantation in Adults with Inborn Errors of Immunity.
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de Winter Janneke J H, Ibrahimov Birtan M, Verheij Frances A, Brinkman Iris D, Stuut Anniek H G, Schonewille Pleun, Heijstek Marloes W, van Rhenen Anna, van der Wagen Lotte E, Daenen Laura G M, Janssen Anke, Hutten Tim J A, Kuball Jürgen, Leavis Helen L, de Witte Moniek A
Аннотация
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.
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.