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Table 1 Overview of the available MRD detection methods in MCL

From: Advances in the assessment of minimal residual disease in mantle cell lymphoma

Feature FC PCR NGS
Target Immunophenotype IgH rearrangement, t(11;14), SOX11, CCND1 Somatic mutations IgH rearrangement Somatic mutations
Detection limit 4-color: 10-3
8-color: 10-4, 10-5
10-5 10-5 10-6 10-6
Turnaround time 3–4 h 2 weeks Less than a week 1 week 1–2 weeks
Strengths -Rapid quantification
-Well validated with low calibration failure
-Robust and accurate
-High sensitivity
-High reproducibility
-Regular quality control rounds
-Theoretical potential for increased sensitivity for low-level clones
-Absolute quantification method
-High sensitivity
-Can detect MRD not identified by multi-parameter FC or qPCR
-Independent of patient-specific primers
-Fast due to universal reagents
-Applicable to all lymphoma subtypes
-Liquid biopsy
-Broad genomic information
-Can track clonal evolution and resistance
Limitations -Comparatively not sensitive
-Not standardized
-Requires presence of circulating tumor cells
-Requires expertise in analysis
-Time consuming
-Primer design necessary
-Non universal reagents
-Assessment limited to few genetic lesions
-Cannot track clonal evolution
-Labor intensive for tumors without canonical translocations
-Not an absolute quantification tool
-Limited capability for multiplexing
-Tracking of clonal evolution limited by throughput
-Requires specialized technology not widely accessible
-ctDNA detection cannot identify the site or extent of disease relapse
-Limited genomic information as it only allows Ig sequencing
-Only tracks Ig-based clonal evolution
-Primary sample required
-Complex bioinformatics evaluation
-Requires tumor tissue for clonotype determination
-Limitation in sensitivity due to breadth of genes and sequencing depth
-Limited detection at low allele frequencies