Tracing Leukemia Stem Cells and Their Influence on Clinical Course of Adult Acute Myeloid Leukemia

Bone marrow samples from 84 adult patients with acute myeloid leukemia (AML) were analyzed using flow cytometry after induction days 14 and 28 for regular minimal residual disease panels and leukemia stem cell panels (CD34/CD123/CD45CD38 and CD90/CD133/CD45/CD33). Leukemia stem cell overexpression was associated with poor survival of patients with AML. Expression of CD123(+)/CD34(-), CD34(+)/CD38(-)/CD123(+), and CD133(+)/CD33(-) and minimal residual disease are sensitive predictors of the clinical course of AML. Background: Acute myeloid leukemia (AML) evolves from neoplastic transformation of stem cell disease termed leukemia stem cells (LSCs). An unsatisfactory response to AML therapy is determined by the presence of minimal residual disease (MRD). The predominance of LSCs might anticipate sustained MRD results. The present study aimed to demonstrate the effect of LSCs on MRD at induction days 14 and 28 on overall survival (OS) and disease-free survival (DFS) and to compare LSC expression with MRD status. Patients and Methods: A total of 84 patients with de novo adult AML underwent testing using LSC panels for CD38/CD123/CD34/CD45 and CD90/CD133/CD45/CD33 and different regular MRD panels. Results: At day 14 after induction, the high expression of CD123 and CD133 had adverse effects on both OS and DFS (P = .004 and P <= .001 and P <= .001 and P <= .001, respectively). Greater expression of CD34(+)/CD38(-)/CD123(+) resulted in unfavorable OS and DFS (P <= .001 for both). Both CD34(+)/CD38(-)/CD123(+) and CD34(-)/CD38(+)/CD123(+) expression at day 14 after induction had an adverse effect on DFS only (P < .001 and P = .029, respectively). On multivariate analysis, CD133 expression and MRD status were independent prognostic parameters (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2-4.4; P = .015; and HR, 2.9; 95% CI, 1.0-7.9; P = .041). At day 28 after induction, MRD and increased CD123(+)/CD34(-), CD34(+)/CD38(-)/CD123(+), CD133(+)/CD33(-) expression were associated with inferior OS (P = .016, P = .0035, P = .0.002, and P = .002, respectively). MRD and high expression of CD34(+)CD123(+), CD133(+)/CD33(-), CD34(+)/CD38(-)/CD123(+) were associated with inferior DFS (P < .001, P = .002, P < .001, P < .001, respectively). On multivariate analysis, only CD133(+)/CD33(-) expression was the independent prognostic factor (HR, 3.1; 95% CI, 1.5-6.7; P = .003). Conclusions: Estimation of LSC expression is a sensitive indicator of the response to therapy in adult patients with AML and might be a better prognosticator than the findings from regular MRD panels. (C) 2020 Elsevier Inc. All rights reserved.