Significance of minimal residual disease in lymphoid malignancies

Modern treatment protocols lead to complete remission (CR) in a considerable proportion of patients with lymphoproliferative disorders. However, many of these patients ultimately relapse, implying that achievement of a clinical CR is compatible with significant amounts of residual malignant cells. Cytogenetic, molecular and immunological techniques that are more sensitive than morphology are increasingly used to assess and quantify minimal residual disease (MRD). Immunological marker analysis allows the detection of aberrant or unusual immunophenotypes, PCR techniques target fusion regions of chromosome aberrations and clone-specific immunoglobulin and T-cell receptor gene rearrangements. The rationale underlying MRD studies is to improve measurement of treatment response, to provide independent prognostic information and to optimise therapeutic strategies. In acute lymphoblastic leukemia (ALL), the MRD based evaluation of initial response to front-line therapy emerged as a highly relevant diagnostic tool, particularly in childhood ALL, where MRD has been shown to be an independent prognostic factor allowing a precise risk group classification. In patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL) the prognostic significance of MRD is still a matter of debate, as the majority of patients remain MRD positive after conventional treatment. This phenomenon has changed with the implementation of new treatment modalities, such as application of monoclonal antibodies, where a significant proportion of patients with NHL converts to MRD negativity and experiences prolonged remission. Whether this molecular remission will translate into a superior overall survival is currently the goal of ongoing prospective studies.