Can leukemic stem cells predict short-term outcome in acute myeloid leukemia? – A prospective cohort study from India
Visaali Sivakumar, Prabhu Manivannan, Smita KayalObjectives:
Acute myeloid leukemia (AML) is a clonal stem cell disorder with impaired differentiation, myeloblast proliferation, and genetic heterogeneity. Although remission is frequently achieved with induction therapy, relapse remains common, partly attributed to therapy-resistant leukemic stem cells (LSCs). Indian data on the prognostic significance of LSCs are limited. This study aimed to quantify LSCs at diagnosis using multicolor flow cytometry (MFC) and evaluate their association with clinico-hematological features and response to induction therapy.
Materials and Methods:
This prospective cohort study (September 2022–January 2024) included newly diagnosed AML patients aged <65 years, excluding therapy-related AML, antecedent myelodysplastic neoplasm, and acute promyelocytic leukemia. Clinical parameters and bone marrow samples were analyzed, and LSCs were quantified by MFC. Eighty-six patients were enrolled, with approximately 40% evaluable for post-induction response.
Statistical analysis:
Receiver operating characteristic curves identified optimal LSC thresholds. Associations were assessed using Mann–Whitney/Kruskal–Wallis and Fisher’s exact tests. Survival was evaluated using Kaplan– Meier analysis with log-rank testing, and prognostic factors using backward stepwise Cox regression.
Results:
The median LSC percentage was 4.5% (range: 0.01–89%). A cutoff of 1% showed high sensitivity but low specificity for predicting remission and induction mortality. LSC% correlated with CD34 expression and abnormal karyotype but not with remission, induction mortality, or overall survival (OS) (median OS: 5.5 months). Age, karyotype, and European LeukemiaNet-2022 risk category were significant prognostic factors.
Conclusions:
LSCs did not predict short-term outcomes in AML; established clinical and genetic factors remained more reliable prognostic indicators. Larger studies with longer follow-up are needed.