Immunological detection of minimal residual disease in acute lymphoblastic leukemia

Assessment of minimal residual disease (MRD) during the first months of therapy gives information on the timely response to treatment, and proves to be a powerful and independent indicator of treatment outcome in patients with acute lymphoblastic leukemia (ALL). Immunological evaluation by flow cytometry (FC) is one of the most attractive approaches to this. The present review summarizes the historical development of the technique over the last 20 years, showing that current methodology is based on the existence of leukemia-associated patterns of asynchrony in antigen expression with respect to normal differentiation or location of occurrence. Such asynchrony allows the sensitive detection of rare malignant cells by multiparametric FC, although completely leukemia-specific antigens for broad application do not exist. Clinical studies proved that the technology should now be applicable to almost all patients with ALL and that immunological MRD results correlate well with outcome. However, based on the available set of FC data, it is yet too early to draw firm conclusions for clinical application. Issues still to be addressed by comprehensive and non-selecting investigations on the basis of the most widely used treatment protocols are whether 1) quantitative data generated by PCR and FC are interchangeable, 2) differences between therapeutic regimens influence the significance of qualitative and quantitative aspects of MRD, and 3) absolute enumeration of MRD bears advantages over the common practice of relative quantification. Concluding remarks further relate to technical issues which may allow to simplify the approach in the future which should augment also its economic efficiency.