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.
OBJECTIVE
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.
From the Departments of Hematopathology.
Juan
J
Ouyang
From the Departments of Hematopathology.
Maitrayee
M
Goswami
From the Departments of Hematopathology.
Jie
J
Peng
From the Departments of Hematopathology.
Zhuang
Z
Zuo
Leukemia, The University of Texas MD Anderson Cancer Center, Houston.
Naval
N
Daver
Leukemia, The University of Texas MD Anderson Cancer Center, Houston.
Gautam
G
Borthakur
From the Departments of Hematopathology.
Guilin
G
Tang
From the Departments of Hematopathology.
L Jeffrey
LJ
Medeiros
From the Departments of Hematopathology.
Jeffrey L
JL
Jorgensen
Leukemia, The University of Texas MD Anderson Cancer Center, Houston.
Farhad
F
Ravandi
From the Departments of Hematopathology swang5@mdanderson.org.
Sa A
SA
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D050660:Core Binding Factors / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis*; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D055815:Young Adult
D050660:Core Binding Factors
Acute myeloid leukemia; Core binding factor; Flow cytometry; Minimal residual disease; qRT-PCR