Minimal residual disease in follicular lymphoma

: Follicular lymphoma (FL) is an indolent disease with a continuously remitting course. Despite improved treatment options, about 20% of patients suffer from early relapse and subsequent death. Several baseline clinical, histological and biological parameters have been identified as risk factors for adverse outcome, but they do not predict response to treatment and are currently not being used for risk adapted treatment strategies. In recent years, minimal residual (detectable) disease (MRD) detection has gained considerable interest as a post-treatment outcome predictor and a considerable amount of data has been generated in the field. MRD integrates preclinical risk factors and their influence on achievement of response, by dynamically monitoring the clearance of lymphoma cells during treatment early feedback on the efficacy of treatment for the individual patient can be achieved as well as the identification of adverse prognostic subgroups. Detectable MRD or kinetics of lymphoma regrowth after the end of treatment (EOT) identifies patients at risk of clinical relapse much earlier than imaging techniques. Therefore, MRD assessment allows a stratification for individualized treatment approaches early in the treatment course and might provide tailored treatment approaches in the future. This review will discuss major technical advances and significant clinical messages that have been derived from the application of MRD monitoring in clinical trials during the last decade. Furthermore, we discuss the prognostic role of combined metabolic response by 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) and molecular MRD analysis at end of induction (EOI) as an endpoint and early read-out in clinical trials. 16