ASH 2025 | A case report used to evaluate gene therapy outcomes in transfusion-dependent β-thalassemia

This abstract is an abstract concerning our first TDT France and Europe patient treated by gene therapy approach by CRISPR-Cas9. You know that this approach offers transformative potential for transfusion-dependent thalassemia, but safety concerns remain regarding the clonal hematopoiesis and residual hemolysis after graft. This report presents the first French TDT patient, as I said, treated with a gene therapy and monitored for efficacy and clonal hematopoiesis evolution. It’s a 35-year-old patient with a severe TDT who underwent autologous gene therapy after a splenectomy and busulfan conditioning. The post-gene therapy showed that patient became transfusion-independent. The hemolysis biomarkers improved dramatically with a plus heme who dropped by 98.5% and hemopexin was normalized. The gene editing efficiency reached 66.9% at 16 weeks of follow-up with no clonal dominance or structural rearrangement. And the pre-existing DNMT3A mutation remained stable at low frequency, suggesting no clonal expansion. The gene therapy achieved in this patient a robust hematologic correction and hemolysis improvement without evidence of clonal risk in the short term of follow-up. In conclusion, clonal hematopoiesis screening remains essential for patient selection and long-term monitoring.

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