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 15^th 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.

Abstract

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.