Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contributeto postinduction treatment stratification

Early response to therapy is one of the most important prognostic factors i n acute leukemia. It is hypothesized that early immunophenotypical evaluati on may help identify patients at high risk for relapse from those who may r emain in complete remission (CR). Using multiparametric flow cytometry, the level of minimal residual disease (MRD) was evaluated in the first bone ma rrow (BM) in morphologic CR obtained after induction treatment from 126 pat ients with acute myeloid leukemia (AML) who displayed aberrant phenotypes a t diagnosis. Based on MRD level, 4 different risk categories were identifie d: 8 patients were at very low risk (fewer than 10(-4) cells), and none hav e relapsed thus far; 37 were at low risk (10(-4) to 10(-3) cells); and 64 w ere at intermediate risk (fewer than 10(-3) to 10(-2) cells), with 3-year c umulative relapse rates of 14% and 50%, respectively. The remaining 17 pati ents were in the high-risk group (more than 10(-2) residual aberrant cells) and had a 3-year relapse rate of 84% (P = .0001). MRD level not only influ ences relapse-free survival but also overall survival (P = .003). The adver se prognostic impact was also observed when M3 and non-M3 patients with AML were separately analyzed, and was associated with adverse cytogenetic subt ypes, 2 or more cycles to achieve CR, and high white blood cell counts. Mul tivariate analysis showed that MRD level was the most powerful independent prognostic factor, followed by cytogenetics and number of cycles to achieve CR. In conclusion, immunophenotypical investigation of MRD in the first BM in mCR obtained after AML induction therapy provides important information for risk assessment in patients with AML. (C) 2001 by The American Society of Hematology.