AML-230 predictive value of CD34-positive versus CD34-negative leukemic stem cells on survival outcome in acute myeloid leukemia

Abstract

Context: Leukemic stem cells (LSCs) have emerged as a potential factor contributing to an overall dismal outcome in acute myeloid leukemia (AML). Objective: In this study, using flowcytometric immunophenotyping (FCMI), we have demonstrated LSC identification and quantification in both the CD34+ and CD34–compartments to find its relevance in predicting treatment outcomes. Furthermore, we correlated the impact of LSC quantification at diagnosis as a predictor of long-term survival. Design: This is a prospective analysis of patients diagnosed with AML (per standard WHO criteria). Setting: Tertiary care cancer center. Patients: A total of 161 patients with a diagnosis of non–acute promyelocytic leukemia (non-APL) AML patients diagnosed over a period of two years (January 2019 to December 2020) were evaluated. Interventions: Bone marrow aspirates collected in EDTA were processed for FCMI using a stain-lyse-wash technique with a singletube, 10-color comprehensive antibody panel. LSCs were identified primarily in the CD34+CD38– compartment; however, in a substantial number of CD34– AML, LSCs were segregated from the CD34–CD38- compartment using CD117 as an alternate gating marker and CD123, CD33, and CD11b as LSC-specific markers in all cases. Main Outcome Measures: 1. CD34+ versus CD34–LSC and 2. Baseline LSC% as a predictor of survival. Results: LSCs were identified in 82.6% (133/161) of patients. CD34+ LSCs and CD34– LSCs were isolated in 82.53% (104/126) and 82.85% (29/35) of cases, respectively. The median survival times (in weeks) in CD34– LSCs was higher than in CD34+ LSCs; EFS (54 vs. 47; P=0.27), RFS (79 vs. 48; P=0.14), and OS (121 vs. 71; P=0.41) were found to be comparable in both groups. Furthermore, the total study cohort was divided into three groups based on diagnostic LSC percentage, i.e., LSC^neg (LSC% <0.004%), LSC^low (LSC%=0.004%–0.892%), and LSC^high (LSC% >0.892%). The LSC^high group had significantly shorter OS, EFS, and RFS compared to the LSC^low and LSC^neg groups. Conclusions: This study confirms the presence of LSCs beyond the usual CD34+CD38– compartment; however, there is no difference in survival outcomes in both groups. Also, LSC quantification is a powerful and independent prognostic parameter in AML predicting long-term survival and risk of relapse.