Choice of a different donor reduces relapse risk after second allogeneic SCT for MDS

Myelodysplastic neoplasms (MDS) relapsing after allogeneic stem cell transplantation (alloSCT) have a poor prognosis. A second alloSCT (alloSCT2) can offer durable remission, however, earlier studies reported <20% long-term survival. Here we summarize contemporary outcome and risk factors after alloSCT2 (2012-2023), particularly focusing on donor change (DoC). We included 313 adults undergoing alloSCT2 for MDS relapse. Donors for alloSCT2 were matched- related/unrelated/haploidentical in 19%/62%/19%, with DoC reported in 71%. Two-year overall-/progression-free survival (OS/PFS), cumulative relapse incidence (RI) and non-relapse mortality (NRM) from alloSCT2 were 45%/33%/37%/30%. Outcome improved over time (2y-OS/PFS: 51%/39% in years 2018-2023). In multivariable analyses, DoC was associated with lower risk of relapse (HR=0.56, 95%-CI: 0.36-0.89), a finding never observed after alloSCT2 for acute leukemia. Additionally, adverse cytogenetics were correlated with relapse risk (HR=1.93, 95%-CI: 1.18-3.17). Risk of NRM decreased in more recent years (HR=0.88, per year later) and in patients with Karnofsky performance score (KPS) ≥90 at alloSCT2 (HR=0.59). Concerning survival, remission after alloSCT1 ≥12 months (HR=0.62/0.67) and KPS ≥90 (HR=0.68/0.69) were associated with better OS/PFS. In summary, we report improved outcomes of alloSCT2 in MDS in more recent years and demonstrate superior disease control by DoC, although a trend toward increased NRM precluded a significant survival benefit.