General AML

Treosulfan-based conditioning regimen improves the long-term survival of AML patients receiving allogenic HCT

Allogeneic Hematopoietic Cell Transplantation (allo-HCT) is a successful treatment used for patients with Acute Myeloid Leukemia (AML) but high relapse rates and toxicity have hindered long-term survival. Conditioning regimens are a method of improving allo-HCT outcomes for AML patients by providing immunosuppressant and antileukemic effects whilst maintaining a low toxicity profile.

In an article published in Cancer on 15th July 2017, Arnon Nagler  from the Chaim Sheba Medical Center, Israel, and colleagues reported results from their study which assessed the safety and efficacy of  treosulfan-based conditioning regimen in Acute Myeloid Leukemia (AML) patients who had undergone allo-HCT. Treosulfan is an alkylating agent related to busulfan.

In this retrospective study, 520 AML (median age = 57 years) patients receiving allo-HCT and treosulfan-based conditioning between 2000–2012 reported to the European Society for Blood and Marrow Transplantation (EMBT) Acute Leukemia Working Party registry were analyzed.  

The key results of the analysis were:
  • At the median follow-up of 61 months
    • 5-year Overall Survival (OS) = 38%
    • 5- year Leukemia Free Survival (LFS) = 33%
    • 5-year Relapse incidence = 42%
    • 5-year Non Relapse Mortality (NRM) rates = 25%
  • 11 patients (2%) developed veno-occlusive disease with death occurring in 2

The registry analysis showed that long-term survival was improved for AML patients treated with treosulfan-based conditioning regimens. Additionally, this regimen also demonstrated a “favourable NRM and very low risk of veno-occlusive disease” in AML.

 The authors suggested that prospective studies are required in order to optimize treosulfan-based conditioning regimens in AML patients.


BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20-73 years). Donors were human leukocyte antigen-identical siblings (n 5 187), unrelated donors (n 5 235), or mismatched related donors (n 5 98). Conditioning regimens included treosulfan (42 g/m2 [n 5 396], 36 g/m2 [n 5 109], or 30 g/ m2 [n 5 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n 5 52; peripheral blood, n 5 468). RESULTS: At a median follow-up of 61 months, the 5-year overall survival, leukemia-free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II-IV acute and chronic graft-versus-host disease was 24% (grade III-V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno-occlusive disease, with two deaths (0.4%) from veno-occlusive disease. CONCLUSIONS: Treosulfan-based conditioning regimens provide an acceptable long-term survival with favorable nonrelapse mortality and a very low risk of veno-occlusive disease. Further studies are needed to optimize the treosulfan-based conditioning regimen for patients with AML.

  1. Nagler A. et al. Long-Term Outcome After a Treosulfan-Based Conditioning Regimen for Patients With Acute Myeloid Leukemia: a Report From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer. 2017 Jul 15; 123(14): 2671–2679. DOI: 10.1002/cncr.30646.