Abstract
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.
