Efficacy and safety of low-dose TBI combined MAC regimen for HSCT in high-risk AML patients with active disease

The management of high-risk acute myeloid leukaemia (AML) remains challenging, highlighting the need for innovative conditioning strategies beyond current regimens. In the present single-arm study, a FACT regimen comprised of low-dose total body irradiation (TBI) with fludarabine, cytarabine and cyclophosphamide was employed to treat cytogenetically high-risk AML patients exhibiting pre-transplant active disease. This clinical trial is registered in the Chinese Clinical Trial Registry with the registration number ChiCTR2000035111. In this study, 21 high-risk AML patients with pre-transplant disease statuses including primary induction failure, relapse and measurable residual disease positivity, were enrolled to undergo FACT conditioning. The FACT group demonstrated a 1-year non-relapse mortality (NRM) rate of 9.5%, indicating a similar level of safety and tolerability among the conditioning regimens. The estimated cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) at one year was 30.7%. Additionally, the cumulative incidence of chronic GVHD was 36.0% at one year and increased to 43.0% at two years. The FACT regimen is an effective myeloablative conditioning (MAC) strategy for high-risk AML patients, potentially reducing relapse risk without increasing NRM, warranting further research.

高危急性髓系白血病（acute myeloid leukaemia, AML）的诊疗仍面临诸多挑战，凸显了开发超越现有方案的新型预处理策略的迫切需求。本项单臂研究中，研究人员采用由低剂量全身照射（total body irradiation, TBI）联合氟达拉滨、阿糖胞苷与环磷酰胺组成的FACT预处理方案，对存在移植前活动性疾病的细胞遗传学高危AML患者进行治疗。本临床试验已在中国临床试验注册中心（Chinese Clinical Trial Registry）注册，注册编号为ChiCTR2000035111。本研究共纳入21例存在移植前疾病状态（包括原发诱导失败、复发及可测量残留病（measurable residual disease, MRD）阳性）的高危AML患者，接受FACT预处理。FACT组的1年非复发死亡率（non-relapse mortality, NRM）为9.5%，表明该预处理方案的安全性与耐受性处于相似水平。预估的1年2~4级急性移植物抗宿主病（acute graft-versus-host disease, GVHD）累积发生率为30.7%。此外，慢性移植物抗宿主病的1年累积发生率为36.0%，2年时升至43.0%。FACT预处理方案是一种针对高危AML患者的有效清髓性预处理（myeloablative conditioning, MAC）策略，可在不增加非复发死亡率的前提下降低复发风险，值得开展进一步研究。