The use of receiver operating characteristic analysis for detection of minimal residual disease using five-color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse.
BACKGROUND
Multiparameter flow cytometry (MFC) has been shown to be a useful approach for detection of minimal residual disease (MRD). The aim of the study was to determine the optimal threshold that can separate patients into two groups in terms of leukemic residual cells and relapse status after induction and consolidation chemotherapy.


METHODS
Five-color MFC and receiver operating characteristics (ROC) analysis were used to determine the optimal threshold. This study analyzed 54 acute myeloid leukemia (AML) patients.


RESULTS
LAPs were detected in 51/54 (94%) patients. MRD was evaluated in the bone marrow (BM) in morphologic complete remission from 25 and 22 patients after induction and consolidation, respectively. The threshold discriminating MRD(-) from MRD(+) cases was set at 0.15% residual leukemic cells, a level that allowed optimal sensitivity and specificity for prediction of relapse, both at postinduction (P = 0.05) and postconsolidation (P = 0.009) time points using ROC analysis. MRD level postinduction not only influenced relapse-free survival (RFS) (P = 0.004) but also overall survival (OS) (P = 0.003). Multivariate analysis showed that MRD level postinduction was a powerful independent prognostic factor for both RFS (P = 0.037) and OS (P = 0.026).


CONCLUSIONS
Using the ROC analysis, the threshold of 0.15% was defined as the optimal value in discriminating risk categories in AML, and postinduction MRD assessment is able to better predict disease outcome than consolidation. Therefore, MRD analysis by MFC could be used for refining the selection of therapeutic strategies and improving clinical outcome in individual patients.
Al-Mawali
Adhra
A
Institute of Medical and Veterinary Science, Adelaide, Australia.
Gillis
David
D
Lewis
Ian
I
D000328:Adult; D000368:Aged; D024221:Antineoplastic Protocols; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology; D002452:Cell Count / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D055502:Secondary Prevention; D012815:Signal Processing, Computer-Assisted; D015996:Survival Rate; D055815:Young Adult