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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

Name

MFC

qPCR

ddPCR

IgNGS

mutNGS

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

-Availability

-Well validated with low calibration failure

-Robust and accurate

-High sensitivity

-High reproducibility

-Regular quality control rounds

-Fast

-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

-Availability

-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