A novel conditioning regimen of thiotepa combined with low-dose cyclophosphamide for haploidentical hematopoietic stem cell transplantation in pediatric patients with severe aplastic anemia: a prospective study from China

High-dose cyclophosphamide(Cy)-related cadiotoxicity(CT) during transplant conditioning in severe aplastic anemia is a life-threatening complication. Despite the adoption of low dose Cy regimens, severe CT still occurred in practice. To address it, we designed a single-arm prospective clinical trial to evaluate the efficacy and safety of a modified conditioning regimen for reducing CT in high-risk pediatric SAA patients undergoing haploidentical HSCT (haplo-HSCT). The regimen was as follows: Busulfan(Bu) 3.2mg/Kg on days -8 to -7，thiotepa(TT) 10mg/Kg on day -6，Cy80mg/Kg on days -5 to -2 and anti-thymocyte globulin(ATG) 10mg/kg on days -5 to -2.Historical high-risk SAA patients who received the traditional Bu and Cy _{200mg/Kg on days -5 to -2(Bu/Cy high ) Regimen were enrolled as the control group. Our results demonstrated that no severe CT was observed in the novel regimen group(Bu/Cy low TT). The 1-year overall Survival (OS) rate was significantly higher in BuCy low TT group(100%vs.86.1%, P =0.021). No Graft failure (GF) or severe adverse events were observed in the Bu/Cy low TT group. All patients achieved early granulocyte and plantlet engraft. The incidences of grade II-IV and grade III-IV acute graft-versus-host disease (aGVHD) were comparable between the two groups (33.7% vs. 28.6%, P=0.455; 13.9% vs. 5.56%, P=0.285). Univariate analysis of 1-year OS indicated that prior ATG treatment and different conditioning regimen may affect the final outcomes. In conclusion, the BuCy low TT regimen represents a promising alternative choice for pediatric SAA patients at high risk of CT undergoing haplo-HSCT.}