In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established, independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in remission after myeloablative conditioning (MAC; n=515) or non-MAC (n=295) who underwent multiparameter flow cytometry-based MRD testing before and 20-40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85/104 [81.7%]) than non-MAC (33/57 [57.9%]) regimen (P=0.002). Although non-MAC regimens were less likely to clear MRD, if they did the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and "MRD conversion" for relapse (P=0.020), RFS (P=0.002), and OS (P=0.001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared to the isolated use of pre-HCT MRD status and post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments.

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