Allogenic HSCT remains the only curative approach for thalassemia major. We describe results of a

cost-conscious and highly effective matched sibling transplantation strategy for thalassemia major

and sickle cell disease.

We retrospectively analyzed 113 patients who underwent matched sibling donor hematopoietic

stem cell transplantation (HSCT) between February 2022 and June 2025 at two centers in India. The

conditioning regimen included an initial course of fludarabine (Flu) 200 mg/m² and dexamethasone

125 mg/m² administered over 5 days. After a 3-week interval, patients received fludarabine 180

mg/m² over 6 days, oral busulfan (Bu) 14 mg/kg over 4 days, and intravenous cyclophosphamide

(Cy) 200 mg/kg over 4 days. This was followed by infusion of granulocyte colony-stimulating

factor (G-CSF)–primed bone marrow. Graft-versus-host disease (GVHD) prophylaxis consisted of

cyclosporine and methotrexate (MTX).

Out of 113 patients, the male to female ratio was approximately 2:1, with 74 and 39 males and 39

females, respectively. The median age at transplantation was 8.1 years (IQR 6–11; range, 2–16.5

years). The median time to neutrophil engraftment was 18 days (IQR 16–21), and for platelet

engraftment, 20 days (IQR, 18–24). At a median follow-up of 12.2 months (IQR, 6–19), overall

survival (OS) was 95.6%, thalassemia-free survival (TFS) was 93.9%, and graft-versus-host disease

(GVHD)-free survival was 93.1%. Graft failure occurred in 2 patients (1.7%), and mixed chimerism

was observed in 21 patients (18.5%). Acute GVHD grade ≥3 occurred in four patients (3.5%), while

no patients developed moderate or severe chronic GVHD. 20 patients (17.6%) had Subclinical

cytomegalovirus (CMV) reactivation, and CMV disease in 1 patient (0.8%). Veno-occlusive disease

(VOD) developed in nine children (8%), all were managed with supportive care. Transplant-related

mortality (TRM) was 4.4% (5 patients), with four deaths prior to engraftment: one due to

intracranial hemorrhage and three due to septic shock and one death post-engraftment due to acute

liver failure. The average total cost of this transplantation approach was approximately USD 9,600

per patient.

Early results from our study demonstrate that very high GVHD-free and thalassemia/sickle cell

disease-free survivals can be achieved in matched sibling transplantation with a cost-contained

approach utilizing widely available drugs.

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2025
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