Novel FABT-Based Conditioning Regimen With Haploidentical Transplantation for Severe Aplastic Anemia: A Prospective, Single-Center, Phase II Clinical Trial

Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an alternative treatment for severe aplastic anemia (SAA) patients who undergo transplantation lacking a suitable HLA-identical sibling donor. However, its development has been hindered by graft failure and severe graft-versus-host disease (GVHD). We conducted a prospective study to evaluate the efficacy of the FABT (Fludarabine-ATG-Busulfan-Thiotepa) regimen for aplastic anemia (AA) in Haplo-HSCT. This regimen introduced thiotepa into the protocol for the first time, combined with low-dose ATG (2 mg/kg/day) and the post-transplant cyclophosphamide (PTCy) regimen to prevent GVHD. From April 2022 to June 2024, 36 eligible AA patients were recruited for the study, with a median follow-up duration of 21 (2 to 30) months. None of the 36 patients experienced primary graft failure, and the engraftment rates for neutrophil (NE) and PLT were 100% and 91.7%, respectively. The median time to platelet (PLT) and NE engraftment was 13 (8 to 27) and 14 (8 to 21) days, respectively. The 2-year cumulative incidence of CMV reactivation was only 11.1%, and no CMV disease was observed. The incidence of aGVHD and grade II to IV aGVHD was 27.8% and 8.3%, respectively. Additionally, the incidence of cGVHD was 11.1%, all of which were mild cutaneous rejection. The 2-year OS and 2-year GVHD relapse-free survival (GRFS) were both 91.7%. Surprisingly, patients under 40 years old have a 2-year OS of 100%. Compared to the traditional Baltimore regimen, this approach reduced the incidence of aGVHD, cGVHD, and CMV reactivation, while improving OS and GRFS, which may offer a new option for Haplo-HSCT in AA patients.