Reduced‐dose post‐transplant cyclophosphamide plus low‐dose post‐transplant anti‐thymocyte globulin as graft‐versus‐host disease prophylaxis with fludarabine–busulfan–cytarabine conditioning in haploidentical peripheral blood stem cell transplantation: A multicentre, randomized controlled clinical trial

Summary Anti‐thymocyte globulin (ATG) or post‐transplant cyclophosphamide (PTCy)‐based regimens are widely used for graft‐versus‐host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo‐HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo‐PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced‐dose PTCy (40 mg/kg/d on days 3 and 4) combined with low‐dose post‐transplant ATG (2.5 mg/kg on day 8)‐based GVHD prophylaxis (reduced‐dose PTCy/ATG) with fludarabine–busulfan–cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced‐dose PTCy/ATG or a standard‐dose ATG group (‘Beijing Protocol’, ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II–IV (11.5% vs 39.3%, p = 0.001) and grade III–IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced‐dose PTCy/ATG group. Furthermore, two‐year overall survival, disease‐free survival and GVHD‐free/relapse‐free survival were significantly improved in the reduced‐dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low‐dose ATG to reduced‐dose PTCy with FBA conditioning is a promising strategy in haplo‐PBSCT.