IPSS-M downstaging before transplantation does not improve the prognosis of patients with myelodysplastic neoplasms

Allogeneic hematopoietic cell transplantation (ASCT) is the only curative option for patients with myelodysplastic syndromes (MDS), but whether cytoreductive pretreatment and molecular "downstaging" according to the IPSS-M improves outcomes remains unclear. We retrospectively analyzed 128 consecutive adults with MDS who underwent ASCT grouped as frontline transplantation (n = 87) or pretreated before transplant (n = 41). Median bone marrow blasts at diagnosis were 12% vs. 10%. IPSS-M was calculated at diagnosis and immediately before transplant using cytogenetic and next-generation sequencing data. IPSS-M improved in 26% of frontline and 34% of pretreated patients, was unchanged in 41% and 34%, and worsened in 30% and 32%, respectively. After a median follow-up of 17.3 months, overall survival (OS), relapse-free survival (RFS) and graft-versus-host disease relapse-free survival (GRFS) were superior with frontline transplantation (median OS 112.6 vs 14.0 months, p = 0.03, median RFS 61.0 vs 8.9 months, p = 0.007 and median GRFS 13.3 vs 5.3 months, p = 0.004). However, in a landmark analysis starting at the time of transplantation, the difference in OS was no longer statistically significant. Non-relapse mortality was significantly higher after pretreatment (p = 0.018). Pretransplant cytoreduction did not improve post-transplant outcomes despite modest IPSS-M improvements, supporting molecular-risk-guided timing and early donor identification rather than treatment aimed at IPSS-M downstaging.