Identification of prognostic subgroups among acute myeloid leukemia patients with intermediate risk cytogenetics using a flow-cytometry-based assessment of ABC-transporter function.

BACKGROUND: A median fluorescence intensity ratio (MFIR) which measures the efflux of mitoxantrone (an ATP Binding Cassette (ABC) transporter substrate) with and without ABC transporter inhibition correlates with expression of MDR1 and BCRP in acute myeloid leukemia (AML) blasts. METHODS: This study evaluates the impacts of the MFIR on AML outcomes and its interaction with detection of the FLT3 ITD. RESULTS: Among 200 newly diagnosed AML patients, an MFIR of ≥ 1.9 (MFIR+) was detected in 60 (30%) leukemic blast samples. In multivariate analysis, MFIR was an independent prognostic factor for response to induction chemotherapy (OR=7.2, P<0.00001), DFS (HR=2.3, P=0.004) and OS (HR=2.2, P=0.0005) with the main effect being in the 141 patients with intermediate risk cytogenetics. Among intermediate risk cytogenetics patients: MFIR+ outcomes were similar to unfavorable cytogenetic risk (CR, 53% vs. 52%, P=1.0; OS, 11 vs. 9 months, P=0.79). MFIR status can further stratify the prognostic risk for patients with or without FLT3 ITD mutation. CONCLUSIONS: MFIR has value in predicting outcomes including DFS and OS as well as induction failure. This is particularly true for patients with intermediate risk cytogenetics and when combined with assessment for the FLT3-ITD mutation.