Early post-transplant molecular residual disease predicts outcomes in myelodysplastic neoplasms and myelodysplastic neoplasms/acute myeloid leukemia undergoing allogeneic transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative therapy for myelodysplastic neoplasms/syndromes (MDS), but post-transplant relapse continues to limit long-term survival. Reliable identification of patients at high relapse risk remains lacking. A cohort of 192 patients with MDS or MDS/acute myeloid leukemia undergoing allo-HSCT was analyzed to assess the prognostic significance of measurable residual disease (MRD) by next-generation sequencing (NGS) and multiparameter flow cytometry (MFC). MRD was assessed longitudinally at predefined time points; NGS-MRD positivity was defined as persistence of disease-associated mutations (excluding DNMT3A, TET2 , and ASXL1 ) at a variant allele frequency > 0.01%. At 1 month post-transplantation, NGS-MRD positivity was detected in 25.9% of patients and was strongly associated with higher relapse risk and inferior survival outcomes. The 6-month cumulative incidence of relapse was significantly higher in MRD-positive vs. MRD-negative patients (64.7% vs. 23.5%), with markedly shorter relapse-free survival (5.3 vs. 85.3 months) and overall survival (13.4 vs. 73.7 months) (all P  < 0.05). In multivariable analysis, 1-month NGS-MRD positivity remained an independent relapse and mortality predictor. MFC-MRD demonstrated prognostic value only at later time points. Early post-transplantation NGS-MRD may be a dominant prognostic biomarker and support its integration into MRD-guided, risk-adapted post-transplantation management strategies.