ASH 2025 | Screening for clonal hematopoiesis before curative therapy in β-hemoglobinopathies

Thank you to us for this opportunity to let me share with you our abstract concerning this screening for chronic hematopoiesis in beta hemoglobinopathic patients, especially those candidates for curative approach as hematologic stem cell transplantation or gene therapy. Well, you know that allogeneic hematopoietic cell transplantation and gene therapy are curative options for sickle cell disease and transfusion-dependent thalassemia. However, recent evidence showed that clonal hematopoiesis may increase the risk of post-transplant myeloid malignancies. This study emphasized the importance of systematic clonal hematopoiesis screening before transplant. Between 2020 and 2025, 60 patients, including 56 sickle cell disease patients and four transfusion-dependent thalassemia patients, were screened using a targeted sequencing panel. Clonal hematopoiesis was detected in 20% of patients with mutations mainly in DNMT3A, TP53, PPM1D, and ASXL1. Median age for clonal hematopoiesis positive patients was slightly higher, and some patients underwent allo-hematological stem cell transplantation or gene therapy despite this clonal hematopoietic presence. The follow-up showed no secondary malignancies in the entire cohort, and one case of graft rejection occurred without pre-existing clonal hematopoietic detection. Interestingly, a DNMT3A clone was later traced to be part of a sibling donor in one patient. In conclusion, clonal hematopoiesis is frequent in sickle cell disease patients and may influence transplant outcomes. Thus, pre-transplant molecular profiling should become a standard to guide therapy choice and improve the long-term safety. In conclusion, future studies will refine the risk stratification and surveillance strategies.

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