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

## TL;DR

This study shows that a modified stem cell transplant method is feasible and safe for adults with immune system disorders, leading to successful immune recovery and reduced complications.

## Contribution

Demonstrates the feasibility of αβTCR/CD19-depleted allo-HSCT in adults with inborn errors of immunity.

## Key findings

- All patients achieved primary engraftment with no chronic GvHD observed.
- Most patients showed improved immune function and could stop immunoglobulin use.
- Clinical outcomes were encouraging, but larger studies are needed for confirmation.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s10875-025-01978-9.