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

Ann Med. 2025 Dec;57(1):2446692. doi: 10.1080/07853890.2024.2446692. Epub 2024 Dec 28.

Abstract

Background: The management of high-risk acute myeloid leukaemia (AML) remains challenging, highlighting the need for innovative conditioning strategies beyond current regimens.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Acute myeloid leukaemia; allogeneic hematopoietic stem cell transplantation; conditioning regimen; prognosis.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / adverse effects
  • Cyclophosphamide* / therapeutic use
  • Cytarabine* / administration & dosage
  • Cytarabine* / adverse effects
  • Cytarabine* / therapeutic use
  • Female
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Middle Aged
  • Transplantation Conditioning* / methods
  • Treatment Outcome
  • Vidarabine* / administration & dosage
  • Vidarabine* / analogs & derivatives
  • Vidarabine* / therapeutic use
  • Whole-Body Irradiation* / adverse effects
  • Young Adult

Substances

  • Vidarabine
  • fludarabine
  • Cyclophosphamide
  • Cytarabine

Grants and funding

This study is supported by Hangzhou Science and Technology Major Project under Grant Number 202004A15, Hangzhou Medical Health Science and Technology Major Project under Grant Number Z20210039, Zhejiang Province Traditional Chinese Medicine Science and Technology Project under Grant Number 2023ZR122 and National Natural Science Foundation of China under Grant Number 82100200.