Optimizing outcomes and accessibility of matched sibling donor transplant for transfusion dependent thalassemia in...

Severe thalassemia is a life-threatening condition common in many low and middle-income countries. While bone marrow transplantation (BMT) offers a curative option, its accessibility remains limited due to cost and complexity. This study describes a simplified approach to BMT for hemoglobinopathies which is based on relatively common and inexpensive medicines. This study included 176 paediatric patients with transfusion dependent thalassemia who received a matched sibling bone marrow transplant between February 2022 and November 2025 across several centers in Asia and the Middle East. A simplified and low-cost transplant protocol was used, based on drugs that are widely available, and are listed in the WHO Model List of Essential Medicines. The regimen included fludarabine, dexamethasone, busulfan, and cyclophosphamide. G-CSF primed bone marrow was used as the graft source, and GVHD prophylaxis included cyclosporine and methotrexate. Rejection, mixed chimerism rates, transplant-related mortality, and GVHD-free, overall and disease-free survival composite outcome were analysed. Engraftment was obtained in 97.3% of patients. Thalassemia-free survival was 93.4%, and overall survival was 96% at a median follow-up of 11.3 months. Rates of moderate-severe acute GVHD were low (3.9%), for a GVHD-free and thalassemia-free composite actuarial outcome of 93.4%. CMV reactivation was observed in 19.2% of patients and one progressed to CMV disease. The approach was equally effective in experienced and newly established transplant centers. A simple, safe, and cost-conscious transplant approach using generally available medicines can achieve excellent outcomes for children with severe thalassemia in low-resource settings.