Immunologic minimal residual disease detection in acute lymphoblastic leukemia: A comparative approach to molecular testing

The generation of antisera directed against leukocyte differentiation antigens opened the possibility of studying minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL). During the three decades that followed the pioneering studies in this field, great progress has been made in the development of a wide array of monoclonal antibodies and of flow cytometric techniques for rare event detection. This advance was accompanied by an increasingly greater understanding of the immunophenotypic features of leukemic and normal lymphoid cells, and of the antigenic differences that make MRD studies possible. In parallel, molecular methods for MRD detection were established. The systematic application of immunologic and molecular techniques to study MRD in clinical samples has demonstrated the clinical significance of MRD in patients, leading to the use of MRD to regulate treatment intensity in many contemporary protocols. In this article, we discuss methodologic issues related to the immunologic monitoring of MRD and the evidence supporting its clinical significance, and compare the advantages and limitations of this approach to those of molecular monitoring of MRD.