Fludarabine, Busulfan, Thiotepa, and Melphalan: A Novel Low-Toxicity Myeloablative Conditioning Regimen for Haploidentical HSCT in Children and Adolescents Aged ≥7 Years With Transfusion-Dependent β-Thalassemia.

BACKGROUND

Graft failure and transplant-related mortality remain major barriers to haploidentical donor hematopoietic stem cell transplantation (HID-HSCT) in children and adolescents aged ≥7 years with transfusion-dependent thalassemia (TDT). Thus, a novel low-toxicity myeloablative conditioning regimen was developed to improve transplantation outcomes.

METHODS

In this prospective, single-center study (clinical trial registration ChiCTR2300071890), TDT patients aged ≥7 years were enrolled to evaluate the safety and efficacy of a conditioning regimen comprising fludarabine, busulfan, thiotepa, and melphalan (F-BMT). For HID recipients, graft-versus-host disease (GVHD) prophylaxis included half-dose PTCY combined with the in vivo T-cell depletion (porcine anti-human lymphocyte immunoglobulin or rabbit anti-human thymocyte globulin), along with other immunosuppressive agents. The primary endpoint was the 2-year thalassemia-free survival (TFS) rate.

RESULTS

From June 2023 to August 2024, 29 TDT patients aged ≥7 years undergoing HID-HSCT were enrolled (14 males, 15 females). The 2-year TFS and overall survival rates were both 93.1%. Neutrophil and platelet engraftment were achieved in all patients, with no reported graft failure. The observed incidence of Grade II-IV acute GVHD was 17.2%. Chronic GVHD occurred in 6.9% of the patients. Regimen-related toxicities were manageable, with only one case of sinusoidal obstruction syndrome and three cases of hemorrhagic cystitis, all of which resolved with supportive treatment. No mixed chimerism was observed.

CONCLUSIONS

The F-BMT regimen provides effective myeloablation with reduced toxicity, supporting its feasibility for HID-HSCT in TDT patients aged ≥7 years.