Personalized Circulating Tumor DNA (ctDNA) Profiling Enables Superior and Universal Measurable Residual Disease (MRD) Detection in Acute Myeloid Leukemia (AML)

Relapsed and/or refractory disease remains the leading cause of death in AML, highlighting the need for broadly applicable, high-sensitivity approaches to MRD detection. We developed AML-CAPP-Seq ( Ca ncer P ersonalized P rofiling by Deep Seq uencing), a personalized hybrid-capture assay that tracks both canonical AML drivers and patient-specific variants identified by whole-exome sequencing. In 56 patients with longitudinal plasma and matched peripheral blood and bone marrow samples, AML-CAPP-Seq enabled universal MRD assessment and resolution of clonal dynamics using a median of 30.5 variants per patient. Plasma ctDNA outperformed cellular compartments for MRD detection and more strongly predicted relapse-free (HR 17.8, p