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.
Richardson et al. (Tue,) studied this question.