Haploidentical αß T-cell Depleted Stem Cell Transplantation in Pediatric Beta-Thalassemia

Overview

This study evaluates the feasibility, safety, and efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with αß T-cell depletion in 20 pediatric and young adult patients with transfusion-dependent beta-thalassemia (TDT). Results suggest that TCRαß/CD19+ depleted haplo-HSCT is a promising alternative to matched sibling donor (MSD) HSCT, especially when MSDs are unavailable.

Background

Beta-thalassemia is a genetic disorder characterized by reduced or absent β-globin synthesis, leading to ineffective erythropoiesis and transfusion dependency. Lifelong transfusions cause iron overload and organ damage, reducing quality of life and life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) from matched donors is the current curative standard but is limited by donor availability and complications related to iron overload and graft failure. Haploidentical HSCT with αß T-cell depletion offers an alternative approach with potentially lower graft-versus-host disease (GvHD) rates.

Data Highlights

Key Findings

• Haplo-HSCT grafts were successfully depleted of αß T-cells and CD19+ B cells, achieving targeted cell doses.
• Patients with no matched donor available received haplo-HSCT with comparable conditioning regimens using treosulfan-based protocols.
• Pesaro classification distribution included patients across classes I to III, indicating a range of iron overload severity.
• Pre-transplant donor-specific antibody screening and donor selection prioritized absence of DSA to reduce graft failure risk.
• Two patients underwent haplo-HSCT as second transplants following graft failure from previous HSCTs.
• No pretransplant pharmacologic immunosuppression was applied prior to conditioning.

Clinical Implications

Haploidentical HSCT with αß T-cell depletion represents a viable curative option for pediatric and young adult patients with transfusion-dependent beta-thalassemia lacking matched sibling donors. The use of treosulfan-based conditioning and careful donor selection including DSA screening may reduce transplant-related complications and graft failure. This approach may expand access to curative therapy in populations with limited donor availability.

Conclusion

TCRαß/CD19+ depleted haploidentical HSCT is a feasible and safe alternative to matched sibling donor transplantation in pediatric and young adult patients with transfusion-dependent beta-thalassemia, warranting further prospective evaluation.

References

1. IthaGenes Database/2024 -- Beta-thalassemia mutations and clinical overview
2. Cappellini et al./2020 -- Management of beta-thalassemia: current standards and future prospects
3. Lucarelli et al./2018 -- Hematopoietic stem cell transplantation in beta-thalassemia
4. Locatelli et al./2013 -- HSCT for thalassemia: matched sibling donor outcomes
5. Angelucci et al./2017 -- Cost-effectiveness of HSCT in thalassemia
6. Thuret et al./2019 -- Outcomes of matched donor HSCT in children with TDT
7. Gaziev et al./2016 -- Age impact on HSCT outcomes in beta-thalassemia
8. De la Fuente et al./2021 -- Adult HSCT outcomes in beta-thalassemia
9. Borgna-Pignatti et al./2014 -- Donor availability in thalassemia HSCT
10. Locatelli et al./2018 -- Ethnic disparities in donor matching
11. Lucarelli et al./2015 -- Graft failure risk factors in thalassemia HSCT
12. Shah et al./2020 -- Haploidentical HSCT approaches in non-malignant diseases
13. Fischer et al./2022 -- Outcomes of TCRαß/CD19+ depleted haplo-HSCT in TDT
14. Sorror et al./2017 -- Iron overload and organ damage in HSCT
15. Carreras et al./2019 -- Sinusoidal obstruction syndrome in HSCT
16. Balashov et al./2021 -- Haplo-HSCT with post-transplant cyclophosphamide
17. Locatelli et al./2020 -- Ex vivo T-cell depletion in haplo-HSCT
18. Ciurea et al./2018 -- Post-Cy haplo-HSCT outcomes
19. Fischer et al./2021 -- GvHD incidence in haplo-HSCT for non-malignant diseases
20. Locatelli et al./2023 -- Treosulfan conditioning in haplo-HSCT
21. EudraCT No. 2018-002652-33 -- Treosulfan in haplo-HSCT for sickle cell disease
22. Ishak et al./1995 -- Histological classification of liver fibrosis