Abstract / Summary
Background/Objectives: Severe unstable hemoglobinopathies may cause transfusion dependence from early childhood, and allogeneic hematopoietic cell transplantation (allo-HCT) is the only established curative option. Pediatric experience with allo-HCT for unstable hemoglobinopathies is limited to isolated reports, and long-term outcomes remain poorly characterized. The objective of this study was to characterize the clinical and molecular features, transplant approaches, and long-term outcomes of two Brazilian patients with unstable hemoglobinopathies, in the context of the published pediatric literature. Methods: We performed a retrospective analysis of two children with unstable hemoglobinopathies who underwent allo-HCT at a Brazilian center. PubMed/MEDLINE and Scopus were searched for pediatric cases published between 2002 and 2025 using terms related to unstable hemoglobin variants and hematopoietic transplantation. Published cases were combined with the Brazilian patients to form an aggregated cohort. Clinical, molecular, transplant, and follow-up data were analyzed descriptively. Results: The aggregated cohort included 13 patients and 15 allo-HCT procedures, using matched sibling, haploidentical, and other alternative donors. All patients were transfusion-dependent before transplantation. Two patients required retransplantation after graft failure. At last follow-up, the nine published patients with available outcome data and both Brazilian patients were alive and transfusion independent. The Brazilian patients maintained complete donor chimerism and transfusion independence for 8 and 9 years, the longest follow-up reported in this population. One remained transfusion independent after retransplantation for secondary graft failure. Conclusions: Allo-HCT may achieve durable transfusion independence in children with severe unstable hemoglobinopathies, but the small number of reported cases limits the interpretation of these findings. Our series adds long-term follow-up data supporting this approach and highlights the need for larger, prospective studies to guide donor selection and conditioning strategies in this rare population.