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

Myelodysplastic syndromes (MDS) can progress to AML and often require allogeneic hematopoietic stem cell transplantation (allo-SCT). The sequential FLAMSA-FB regimen, featuring a cytoreductive FLAMSA phase followed by fludarabine-busulfan (FB) conditioning, may enhance disease control. We retrospectively analyzed 106 untreated MDS patients with blasts 5-19% at the University Medical Center Hamburg who received either FLAMSA-FB (n = 45) or standard conditioning (n = 61: Thiotepa-Busulfan (n = 30), Fludarabine-Busulfan (n = 16), Treosulfan-Fludarabine (n = 15)). Median follow-up was 24 months. The FLAMSA group was younger (median age 56 vs. 62, p = 0.02), but baseline IPSS risk scores (p = 0.16) and donor types (p = 0.43) were comparable. Engraftment rates were similar. At two years, overall survival (OS) was 62% with FLAMSA and 68% with standard conditioning (p = 0.92), while progression-free survival (PFS) was 56% vs. 59% (p = 0.92). Non-relapse mortality (22% vs. 25%, p = 0.78) and cumulative incidence of relapse (22% vs. 13%, p = 0.12) did not differ significantly, nor did grade II-IV acute graft-versus-host disease (GVHD). Propensity score matching in 18 pairs confirmed no significant differences in OS, PFS, NRM, or CIR. However, moderate-to-severe chronic GVHD was higher with FLAMSA-FB (50% vs. 17%, p = 0.04). Thus, FLAMSA-FB did not improve transplant outcomes over standard conditioning but was linked to an increased risk of chronic GVHD.