Abstract Background Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have shown a favorable 10-year overall survival rate of approximately 90% in children with aplastic anemia (AA). However, cyclophosphamide-related cadiotoxicity, a serious and potentially fatal complication, remains a major concern during conditioning. Thiotepa, a cell cycle-independent alkylating agent, has shown promising safety and efficacy in retrospective studies involving pediatric AA patients undergoing transplantation. Nevertheless, its role in haplo-HSCT remains unclear, particularly in terms of reducing cyclophosphamide-related cadiotoxicity risk while allowing for cyclophosphamide dose reduction. To address this, we initiated a prospective, single-arm clinical trial to evaluate the safety and efficacy of the thiotepa-based regimen. Method From December 2024 to July 2025, a total of 20 pediatric patients with ≥ 2 cyclophosphamide-related cadiotoxicity risk factors were enrolled. The conditioning regimen included: Busulfan 3.2 g/kg/day on days -8 and -7; thiotepa 10 mg/kg/day on day -6; cyclophosphamide 20 mg/kg/day on day -5 to -2; rabbit anti-thymocyte globulin (rATG) 2.5 mg/kg/day on day -5 to -2. The primary endpoint was the transplant-related mortality (TRM) within 100 days after transplantation. Secondary endpoints included the incidence of cyclophosphamide-related cadiotoxicity, engraftment rate, and incidence of acute graft-versus-host disease (aGVHD). Results As of August 1, 2025, 20 children were enrolled, including 9 with severe AA (SAA) and 11 with transfusion-dependent non-severe aplastic anemia (TD-NSAA). The male-to-female ratio was 9:11, with a median age at transplantation of 7.5 years (range: 3-16 years). The median dose of infused mononuclear cells (MNCs) was 12.23 × 108 /kg (range: 9.48-15.8 × 108 /kg), and the median CD34+ cell dose was 4.23 × 106 /kg (range: 2.05-12.5 × 106 /kg). The median follow-up duration was 130 days (range: 39-231 days), with 13 patients (65%) have exceeded 100 days follow-up period. At last follow-up, all patients were alive, yielding an overall survival (OS) rate of 100%. All children achieved hematopoietic engraftment, with a median time to neutrophil engraftment of 11 days (range: 9-19 days) and a median time to platelet engraftment of 11 days (range: 8-25 days). One patient (5%) developed poor graft function (PGF) on day 101. No cases of moderate or severe cardiotoxicity were observed. Five patients had mild pericardial effusion, with a median onset of 3 days prior to infusion; none required medical intervention. Among the 20 patients, two developed grade III-IV aGVHD, one developed bronchiolitis obliterans syndrome (BOS), one developed Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder (PTLD), and one experienced cytomegalovirus (CMV) infection. ConclusionOur study demonstrates that a thiotepa-containing conditioning regimen with reduced cyclophosphamide is safe and effective in pediatric AA at risk of cadiotoxicity.
Zhang et al. (Mon,) studied this question.