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.

High-dose cyclophosphamide (Cy)-related cardiotoxicity (CT) during transplant conditioning in patients with severe aplastic anemia (SAA) is a life-threatening complication. To evaluate the efficacy and safety of a modified conditioning regimen to reduce CT in pediatric SAA. We conducted a prospective, single-arm clinical trial. The regimen was as follows: busulfan (Bu) 3.2 mg/kg/d on days -8 and -7, thiotepa (TT) 10 mg/kg/d on day -6, Cy 20 mg/kg/d on days -5 to -2, and antithymocyte 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/d on days -5 to -2; BuCyhigh) regimen served as the control group. No severe CT was observed in the novel regimen group (BuCylowTT group). The 1-yr overall survival rate was significantly higher in the BuCylowTT group (100% versus 86.1%, P = .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% versus 28.6%, P = .455; 13.9% versus 5.56%, P = .285). Univariate analysis of the 1-yr overall survival indicated that prior antithymocyte globulin treatment and the conditioning regimen were associated with survival. The BuCylowTT regimen represents a promising alternative for pediatric patients with SAA at high risk of CT undergoing haploidentical hematopoietic stem cell transplantation.