Comparison between multiparameter flow cytometry and WT1-RNA quantification in monitoring minimal residual disease in acute myeloid leukemia without specific molecular targets

Abstract 

Despite a high remission rate, a significant number of patients with acute myeloid leukemia (AML) relapse. Thus, the evaluation of minimal residual disease (MRD) in AML is an important strategy to better identify high risk patients. Most sensitive methodology to detect MRD is molecular polymerase chain reaction (PCR) but its applicability is restricted to AML with leukemia-specific molecular targets (e.g. AML1-ETO, CBFB-MYH11, MLL, FLT-3). In our study, MRD was monitored at different time points with both MFC and WT1-RNA quantification in 23 AML patients who did not present specific molecular targets. As previously published, we considered values of 10⁻³ (0.1%) in MFC and 90 WT1-RNA ×10⁴ ABL copies as optimal thresholds. Receiver operating characteristics (ROC) analysis was used to confirm these data. To realize the methodology that better identify high risk patients, an analysis of sensitivity, specificity, predictive values (PV) and likelihood ratio (LR) was provided and similar results were showed. MRD levels ≥10⁻³ in MFC as well MRD levels ≥90 WT1-RNA copies in RQ-PCR, identify risk groups of patients with poor prognosis. Therefore, MFC and WT1-RNA quantification showed a comparable capacity in terms of technical performance and clinical significance to identify high risk patients who eventually relapsed.

Keywords: Acute myeloid leukemia, Minimal residual disease, Flow-cytometry, Leukemia-associated immunophenotypes, WT1-RNA