Haploidentical haematopoietic stem cell transplantation for thalassaemia major: A phase IV, open-label, single-centre trial.

We report the results of an open-label, single-centre phase 4 clinical trial evaluating haploidentical haematopoietic stem cell transplantation (Haplo-HSCT) in patients with transfusion-dependent thalassaemia (TDT). A total of 134 patients with TDT were enrolled; the median age was 8.7 years (interquartile range [IQR], 6.0-11.7 years; range, 3-20 years). All patients received a uniform conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis included methotrexate (MTX), mycophenolate mofetil (MMF) and tacrolimus. The primary end-point was 2-year overall survival (OS). Median follow-up is 23.4 months (IQR: 11.5-38.7; range: 6.1-81.5). The 2-year OS, event-free survival (EFS) and graft-versus-host disease-free, relapse-free survival (GRFS) rates were 93.4%, 92.6% and 77.5% respectively. The cumulative incidence rates of aGVHD, grade 2-4 aGVHD and grade 3-4 aGVHD were 47.8%, 30.9% and 12.5% respectively. Donor-specific antibodies (DSAs) and male-recipient/female-donor pairing were associated with inferior OS (p = 0.021; p = 0.010) and EFS (p = 0.040; p = 0.020). Hepatomegaly (≥5 cm) was associated with inferior OS (p = 0.037). Collectively, these findings support Haplo-HSCT as a key curative option for TDT patients in the absence of fully matched donors.