Sequential versus standard conditioning in untreated MDS patients with blasts undergoing allogeneic HSCT

Area of Science:

• Hematology
• Oncology
• Transplantation Immunology

Background:

• Myelodysplastic syndromes (MDS) can progress to acute myeloid leukemia (AML), often necessitating allogeneic hematopoietic stem cell transplantation (allo-SCT).
• The sequential FLAMSA-FB regimen, comprising a FLAMSA cytoreductive phase followed by fludarabine-busulfan (FB) conditioning, has been proposed to enhance disease control in MDS patients undergoing allo-SCT.

Purpose of the Study:

• To evaluate the efficacy and safety of the sequential FLAMSA-FB conditioning regimen compared to standard conditioning regimens in untreated MDS patients undergoing allo-SCT.
• To assess outcomes including overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR).
• To investigate the incidence of acute and chronic graft-versus-host disease (GVHD) in patients receiving FLAMSA-FB versus standard conditioning.

Main Methods:

• Retrospective analysis of 106 untreated MDS patients with 5-19% blasts who underwent allo-SCT.
• Patients received either the FLAMSA-FB regimen (n=45) or standard conditioning regimens (n=61), including Thiotepa-Busulfan, Fludarabine-Busulfan, or Treosulfan-Fludarabine.
• Propensity score matching was used to control for baseline differences between groups, with a median follow-up of 24 months.

Main Results:

• No significant differences were observed in two-year OS (62% vs. 68%, p=0.92), PFS (56% vs. 59%, p=0.92), NRM (22% vs. 25%, p=0.78), or CIR (22% vs. 13%, p=0.12) between the FLAMSA-FB and standard conditioning groups.
• Engraftment rates and the incidence of grade II-IV acute GVHD were similar between the groups.
• However, the incidence of moderate-to-severe chronic GVHD was significantly higher in the FLAMSA-FB group (50% vs. 17%, p=0.04).

Conclusions:

• The sequential FLAMSA-FB conditioning regimen did not demonstrate improved transplant outcomes compared to standard conditioning regimens in this cohort of MDS patients.
• While FLAMSA-FB did not impact survival or relapse rates, it was associated with an increased risk of developing moderate-to-severe chronic GVHD.
• Further research may be warranted to explore modifications or alternative strategies to mitigate the risk of chronic GVHD when using FLAMSA-based conditioning in MDS transplantation.