Leukaemic stem cell burden enhances prognostic precision in the non-adverse European LeukemiaNet risk group of acute myeloid leukaemia.

Leukaemic stem cells (LSCs) are chemo-resistant leukaemia-initiating clones that drive refractoriness and relapse in acute myeloid leukaemia (AML). The study evaluated the prognostic significance of LSC burden in treatment naïve AML patients. LSCs were quantified using Next-generation flow cytometry; patients were stratified into LSCneg/low and LSChigh groups based on the median LSC percentage, and correlated with post-induction morphological remission and measurable residual disease (MRD) status, and long-term outcomes including relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS). LSCs were detectable in 93.5% patients, with a median frequency of 0.386%. Patients with LSCneg/low (≤0.386%) had higher rates of complete remission (CR) (p = 0.05) and MRD negativity (p = 0.002). Lower LSC burden was associated with improved RFS, EFS and OS (all p < 0.05) suggesting the prognostic relevance of LSC quantitation in AML. In both Cluster of Differentiation 34 positve (CD34+) and CD34 negative (CD34-) AML, low LSC% was associated with superior survival outcomes (p < 0.05). LSC burden is a strong, independent predictor of response and survival in AML, and its integration with European LeukemiaNet risk-stratification and MRD assessment may enhance risk refinement and individualized therapy.