Baseline IPSS-M vs Pretransplant Risk Downstaging as Prognostic Determinants in MDS Undergoing Allogeneic Transplantation

Risk stratification in myelodysplastic syndromes (MDS) is essential for clinical decision-making, yet the optimal approach to estimate risk for patients undergoing allogeneic stem cell transplantation (alloHSCT) remains uncertain. Whether dynamic changes in risk between diagnosis and post-hypomethylating agent (HMA) therapy improve prognostic accuracy beyond baseline evaluation has not been established. We retrospectively studied 176 HMA-treated patients who underwent alloHSCT, applying the Molecular International Prognostic Scoring System (IPSS-M) at both diagnosis and pre-transplant. The primary endpoint was 4-year progression-free survival (PFS). Overall, dynamic assessment did not improve prognostic performance compared with baseline evaluation. For 4-year PFS, C-indices at diagnosis versus at alloHSCT were 0.6406 versus 0.6377 (p=0.82). Patients with worsening risk after HMA experienced notably inferior outcomes, while those with apparent improvement fared no better than patients with unchanged risk (4-year PFS: 50%, 50%, and 31% for improved, unchanged, and worsening risk, respectively). Apparent IPSS-M improvement before alloHSCT yielded no gains in survival and no reduction in relapse relative to unchanged risk, a pattern consistent among TP53 wild-type patients. Moreover, clearance of TP53 mutations following HMA therapy did not translate into improved post-transplant outcomes. In summary, dynamic reassessment with IPSS-M prior to alloHSCT offers no prognostic advantage over baseline evaluation at diagnosis in HMA-treated MDS patients. Accordingly, risk reduction should not be regarded as a therapeutic goal or trial endpoint, whereas risk progression constitutes an adverse marker that may inform incorporation of post-transplant maintenance strategies or intensified conditioning regimens to improve survival.