Comparison of Multiparameter Flow Cytometry Immunophenotypic Analysis and Quantitative RT-PCR for the Detection of Minimal Residual Disease of Core Binding Factor Acute Myeloid Leukemia

Abstract

Objectives: To examine the value of minimal residual disease (MRD) by multiparameter flow cytometry (MFC) in core binding factor (CBF) acute myeloid leukemia (AML). Methods: We studied 42 patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 and 51 with inv(16)(p13.1q22)/CBFB-MYH11. Tandem MRD analyses by MFC and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed in 281 bone marrow (BM) samples. Results: Grouping qRT-PCR levels as ≤0.01, 0.01 to 0.1, 0.1 to 1, 1 to 10, and >10%, and reporting MFC (sensitivity, 0.1%-0.01%) as positive or negative, κ coefficient test showed no agreement between qRT-PCR and MFC in BM samples obtained postinduction (n = 44, κ = 0.041), and only weak agreement during consolidation (n = 108, κ = 0.083), maintenance/follow-up (n = 107, κ = 0.164), and salvage chemotherapy (n = 24, 0.376). In the post induction BM samples, while qRT-PCR <0.1% was associated with lower and ≥10% with higher AML relapse risk (P =. 035), qRT-PCR between 0.1% to 1% and 1% to 10% failed to predict relapse. In the latter group with intermediate qRT-PCR results, MFC provided prognostic value for relapse (P = 0.006). Conclusions: MFC and qRT-PCR are complementary tests in monitoring CBF AML MRD.