A novel conditioning regimen incorporating low-dose cyclophosphamide and thiotepa for haploidentical hematopoietic stem cell transplantation in pediatric patients with severe aplastic anemia at high risk of cardiotoxicity.

BACKGROUND: High-dose cyclophosphamide (Cy)-related cardiotoxicity (CT) during transplant conditioning in patients with severe aplastic anemia (SAA) is a life-threatening complication. OBJECTIVE: To evaluate the efficacy and safety of a modified conditioning regimen to reduce CT in pediatric SAA. METHODS: We conducted a prospective, single-arm clinical trial. The regimen was as follows: busulfan (Bu) 3.2 mg/kg/day on days -8 and -7, thiotepa (TT) 10 mg/kg/day on day -6, Cy 20 mg/kg/day on days -5 to -2, and anti-thymocyte globulin 2.5 mg/kg on days -5 to -2. Patients with high-risk SAA in a historical cohort who received the traditional Bu/Cy (Cy 50 mg/kg/day on days -5 to -2; BuCyhigh) regimen served as the control group. RESULTS: No severe CT was observed in the novel regimen group (BuCylowTT group). The 1-year overall survival rate was significantly higher in the BuCylowTT group (100% vs. 86.1%, P=0.021). No graft failure or severe adverse events were observed in the BuCylowTT group. All patients achieved early neutrophil and platelet engraftment. The incidence of grades II-IV and III-IV acute graft-versus-host disease was comparable between the two groups (33.7% vs. 28.6%, P=0.455; 13.9% vs. 5.56%, P=0.285). Univariate analysis of the 1-year overall survival indicated that prior anti-thymocyte globulin treatment and the conditioning regimen were associated with survival. CONCLUSIONS: The BuCylowTT regimen represents a promising alternative for pediatric patients with SAA at high risk of CT undergoing haploidentical HSCT.