Clinical relevance of minimal residual disease detection in adult acute myeloid leukemia.
We have used flow cytometry to quantify minimal residual disease (MRD) in 63 patients with acute myeloid leukemia (AML). No significant correlation was found between the level of MRD after induction and disease outcome. After consolidation, a threshold of 3.5 x 10(-4) residual leukemic cells divided the 57 evaluable patients into two distinct groups: the MRDCons(+) and the MRDCons(-) group, with a relapse rate of 81% (22/27) and 27% (8/30), respectively (p = 0.000035). Although not correlated with prognosis, the level of MRD after induction course affected the degree of cytoreduction achieved with consolidation. In fact, the patients who entered a MRDCons(-) status had a median number of leukemic residual cells of 1.8 x 10(-4) after induction; at the same stage, the bone marrow of patients who were in a MRDCons(+) condition harbored a median level of 1.7 x 10(-3) malignant residual cells (p = 0.00073). The MRDCons(+) status also correlated significantly with poor/intermediate risk cytogenetics, MDR1 phenotype, short duration of overall survival, and relapse-free survival (p = 0.024, 0.021, 0.00001, and 0.00001, respectively). In multivariate analysis, the MRDCons(+) status was associated with a high probability of relapse (p < 0.00026) and short duration of relapse free survival (p = 0.008). Stem cell transplantation did not seem to alter the prognostic impact of high levels of MRD after consolidation: within the MRDCons(+) group, the relapse rate after transplant was 78%. Thus, a MRD > or = 3.5 x 10(-4) leukemic cells at the end of consolidation strongly predicts relapse, and is significantly associated with MDR1-positive phenotype and intermediate/unfavorable cytogenetics.