Clinical outcomes of modified post-transplantation cyclophosphamide versus granulocyte colony-stimulating factor/anti-thymocyte globulin-based protocol in alternative donor transplantation for severe aplastic anaemia.

Post-transplantation cyclophosphamide (PTCy) and granulocyte colony-stimulating factor/anti-thymocyte globulin (G-CSF/ATG) are established protocols for alternative donor haematopoietic stem cell transplantation (AD-HSCT) in severe aplastic anaemia (SAA). A modified PTCy (mPTCy) regimen, featuring increased ATG dosing (2.0 mg/kg/day, days -5 to -3) and reduced cyclophosphamide (40 mg/kg/day, days +3 and +4), showed promising outcomes in a prospective study but lacks direct comparison with G-CSF/ATG. This post hoc comparative analysis utilized data from our prospective mPTCy cohort (ChiCTR2000038297, n = 101, plus a 1-year protocol-consistent enrolment extension, n = 56) and a retrospective historical G-CSF/ATG cohort (n = 140) to compare outcomes in AD-HSCT. Both protocols showed similar incidences of engraftment, graft failure and overall survival. Multivariate analysis confirmed reduced risks of 100-day grade II-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.26-0.71, p < 0.001) and 2-year chronic GVHD (HR 0.33, 95% CI 0.17-0.65, p = 0.001), and improved 2-year GVHD, relapse/rejection-free survival (GRFS; HR 0.51, 95% CI 0.32-0.83, p = 0.007) with mPTCy versus G-CSF/ATG. Subgroup analysis revealed superior outcomes with mPTCy in haploidentical-HSCT, while outcomes were comparable between protocols in unrelated donor HSCT. These findings suggest mPTCy superiority over G-CSF/ATG in SAA patients undergoing AD-HSCT, especially haploidentical-HSCT, by reducing GVHD and improving GRFS.