Prospective Study of a Modified Post-Transplantation Cyclophosphamide Regimen for Severe Aplastic Anemia Patients with HLA-Haploidentical Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative modality for severe aplastic anemia (SAA). The availability of haploidentical donors has expanded valid options for SAA; however, previous post-transplantation cyclophosphamide (PTCy)-based protocols for HLA-haploidentical HSCT in SAA patients are associated with relatively delayed neutrophil and platelet engraftment. We prospectively studied HLA-haploidentical HSCT using bone marrow (BM) combined with peripheral blood stem cells (PBSC) as grafts and a modified PTCy regimen for treating SAA. We evaluated the efficacy and safety of this regimen, which had an increased dose (from 4.5 mg/kg to 6.0 mg/kg) and backward-adjusted timing (from day -9 to -7 to days -5 to -3) of antithymocyte globulin (ATG) compared with previous PTCy protocols. Seventy-one eligible patients were included in this prospective study between July 2019 and June 2022. The median time to neutrophil and platelet engraftment was 13 days (range, 11 to 19 days) and 12 days (range, 7 to 62 days), respectively, and the cumulative incidence (CuI) of neutrophil and platelet engraftment was 97.2 ± 2.2% and 94.4 ± 2.9%, respectively. Five patients experienced graft failure (GF), including 2 with primary GF and 3 with secondary GF. The CuI of GF was 7.0 ± 3.1%. A ≥1-year interval between diagnosis and transplantation was a risk factor for the development of GF (HR, 8.40; 95% confidence interval [CI], 1.40 to 50.47; P = .02). No patients developed grade IV acute graft-versus-host disease (aGVHD) or severe chronic graft-versus-host disease (cGVHD). The 100-day CuI of grade II-IV aGVHD was 13.4 ± 4.2%, and the 2-year CuI of cGVHD was 5.9 ± 2.9%. With a median follow-up of 580 days (range, 108 to 1014 days) for 63 survivors, the estimated 2-year overall survival (OS) and 2-year GVHD-free and failure-free survival (GFFS) were 87.3% (95% CI, 79.4% to 96.0%) and 83.8% (95% CI, 74.9% to 93.7%), respectively. In conclusion, the PTCy regimen with an increased dose and backward-adjusted timing of ATG is an effective and feasible choice for treatment with HLA-haploidentical HSCT using BM combined with PBSC as grafts, with a high rate of and faster engraftment, low rate and intensity of aGVHD and cGVHD, and prolonged OS and GFFS.