PREDICTIVE VALUE FOR TREATMENT OUTCOME IN ACUTE MYELOID-LEUKEMIA OF CELLULAR DAUNORUBICIN ACCUMULATION AND P-GLYCOPROTEIN EXPRESSION SIMULTANEOUSLY DETERMINED BY FLOW-CYTOMETRY

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%), P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp(+) as compared with P-gp(-) patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR), A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4)). Twelve of 36 P-gp(+) patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4)). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML. (C) 1995 by The American Society of Hematology.