Allogenic Hematopoietic Stem Cell Transplantation in Children With Transfusion Dependent Thalassemia Using...

Allogenic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment modality in patients with transfusion-dependent thalassemia (TDT). Over the past decade, there has been a shift towards reduced-toxicity conditioning regimens such as Treosulfan-Thiotepa-Fludarabine (TTF) due to its favorable toxicity profile, potent immunosuppression, and myeloablative effects. This study explores the outcomes of TTF-based conditioning in pediatric TDT patients undergoing allogenic HSCT.

This is a single-center retrospective analysis of 74 pediatric patients who underwent allogenic HSCT using the TTF conditioning regimen at our center from January 2017 to May 2025.

The median age at transplant was 6.2 years (range: 1 to 18 y) and Male: female was 1.8:1. Donor types included matched sibling donor (MSD) in 45 patients (60.8%), matched unrelated donor (MUD) in 16 (21.6%), haploidentical donor in 9 (12.2%) and matched related donor (MRD) in 4 patients (5.4%). Pesaro classes I, II, and III were seen in 24 (32.4%), 32 (43.2%), and 18 (24.3%) patients, respectively. Peripheral blood was the stem cell source in all patients. Median stem cell dose was 5.2 million/kg (range: 4.2 to 6.5 million/kg). Four patients (5.4%) had primary graft failure. In the remaining patients, neutrophil and platelet engraftment occurred at a median of 14 days (range: 11 to 25 d) and 18 days (range: 13 to 36 d), respectively. Mixed chimerism was observed in 10 (13.5%) patients, of whom 2 developed secondary graft failure with autologous recovery. Acute and chronic graft-versus-host disease occurred in 25 (33.7%) and 7 (9.4%) patients, respectively. Cytomegalovirus reactivation was seen in 42 patients (56.7%). Six children (8.1%) suffered from veno-occlusive disease. At a median follow-up of 45.2 months (range: 1.5 to 102 mo), 5-year overall and thalassemia-free survival were 82.2% and 77.7%, respectively. Subgroup analysis by Pesaro classification showed 5-year OS rates of 83.9% for class 1+2 and 78.6% for class 3 (P=0.28). Five-year TFS was 82% for class 1+2 and 65.5% for class 3 (P=0.049). When comparing matched sibling and matched related donor transplants with alternate donor transplants (haploidentical and matched unrelated), the 5-year OS and TFS were significantly higher in the matched donor group (95% vs. 57.3%, P=0.001, and 88.3% vs. 57.3%, P=0.024).

TTF conditioning with a peripheral blood stem cell graft is a well-tolerated and effective approach for allogeneic HSCT in thalassemia. It demonstrates reduced toxicity and favorable transplant outcomes, with superior results in the matched family donor setting compared with the alternate donor group, supporting its role as a promising alternative to traditional busulfan-based conditioning regimens.