Baseline IPSS-M vs pretransplant risk downstaging as prognostic determinants in MDS undergoing allogeneic transplantation

ABSTRACT: 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 before transplant. The primary end point 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 vs at alloHSCT were 0.6406 vs 0.6377 (P = .82). Patients with worsening risk after HMA experienced notably inferior outcomes, whereas 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 after HMA therapy did not translate into improved posttransplant outcomes. In summary, dynamic reassessment with IPSS-M before alloHSCT offers no prognostic advantage over baseline evaluation at diagnosis in HMA-treated patients with MDS. Accordingly, risk reduction should not be regarded as a therapeutic goal or trial end point, whereas risk progression constitutes an adverse marker that may inform incorporation of posttransplant maintenance strategies or intensified conditioning regimens to improve survival.