Ultra-high-sensitivity next-generation sequencing–based MRD predicts outcome in intensively treated older patients with acute myeloid leukemia: results from the ALFA-1200 cohort

Measurable residual disease (MRD) has emerged as a robust surrogate of remission depth and long-term outcome predictor in acute myeloid leukemia (AML), and is now recognized as a key biomarker for post-remission risk strati fi cation [1, 2]. Its clinical relevance has been demonstrated across multiple techniques, including multiparameter fl ow cytometry and molecular approaches, and has been incorporated into international recommendations [1]. More recently, ultra-high-sensitivity next-generation sequencing (UHS-NGS) has enabled the simultaneous tracking of multiple leukemia-associated mutations at very low variant allele frequencies, further re fi ning MRD assessment [3 – 5]. Most of the evidence supporting the prognostic value of UHS-NGS has however been generated in cohorts of younger AML patients treated with intensive chemotherapy [3, 4]. In contrast, older individuals, who account for a substantial proportion of AML cases,havefrequentlybeenexcludedfromthesestudies,orremainunder-represented,largelybecausecomorbiditiesprecludetheuse ofintensivetreatmentapproaches.AMLsarisinginolderpatientsarecharacterizedbydistinctmolecularandclonalfeatures,which mayin fl uence both MRD detectability and prognostic interpretation. Consequently, dedicated clinical data supporting the use and interpretation of UHS-NGS in older patients remain limited, and its applicationinthispopulationhasbeenguidedbyexpertconsensusratherthanrobustprospectiveevidence