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After 25 years, evaluation of minimal residual disease (MRD) in follicular lymphoma (FL) has become a standardized technique frequently integrated into clinical trials for its consistent and independent prognostic significance. Achievement of a sustained MRD negativity is a marker of treatment sensibility that has been associated with excellent clinical outcome in terms of clinical response and progression-free survival, independently from the employed therapy. However, no survival advantages have been reported for MRD negative patients and despite the compelling results of clinical trials, MRD evaluation has currently no role in clinical practice. Ongoing clinical trials will help in clarifying the potential setting in which MRD monitoring may have a routine clinical application i.e. allowing de-escalation of standard maintenance therapy in very low risk patients. In this review the clinical implications of MRD monitoring in Rituximab-era are discussed in light of the current treatment paradigms most aimed at reducing toxicities, and the response definition that now routinely integrates PET scan.
|Figure 1. Diagram of breakpoint sites of the IGH/BCL2 translocation. In most cases the breakpoints of the IGH/BCL2 translocation are located downstream of the coding portion of the BCL2 gene and the IGH locus is mostly involved within the DJ recombination. In about 50% of cases the breaks occur in a 150-bp region in the 3′ noncoding portion of the third exon of the BCL2 gene, named the major breakpoint region (MBR). The other less frequent breakpoints include the minor breakpoint region (mcr), the intermediate cluster region (icr), the 3′ BCL2 and 5′ mcr regions accounting for 5-10%, 5-10%, 6% and 1% of the cases, respectively.|
Clinical Implication of Minimal Residual Disease Monitoring
Current Issues and Future Perspective