Minimal residual disease studies by flow cytometry in acute leukemia

Minimal residual disease (MRD) assays are increasingly important in the clinical management of patients with acute leukemia. Among the methods available for monitoring MRD, flow cytometry holds great promise for clinical application because of its simplicity and wide availability. Several studies have demonstrated strong correlations between MRD levels by flow cytometry during clinical remission and treatment outcome, lending support to the reliability of this approach. Flow-cytometric detection of MRD is based on the identification of immunophenotypic combinations expressed on leukemic cells but not on normal hematopoietic cells. Its sensitivity depends on the specificity of the immunophenotypes used to track leukemic cells and on the number of cells available for study. Immunophenotypes that allow detection of 1 leukemic cell in 10,000 normal cells can be identified in at least 90% of patients with acute lymphoblastic leukemia; immunophenotypes that allow detection of 1 leukemic cell in 1,000-10,000 normal cells can be identified in at least 85% of patients with acute myeloid leukemia. Identification of new markers of leukemia by gene array technology should lead to the design of simple and reliable antibody panels for universal monitoring of MRD. Here we review the relative advantages and disadvantages of flow cytometry for MRD studies, as well as results obtained in correlative studies with treatment outcome.