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Table 1 Advantages and disadvantages of MRD detection methods

From: Minimal residual disease in multiple myeloma: current status

Techniques Sensitivity Advantages Disadvantages
--- Identification of MM cells by Flow cytometry analysis of MM-specific cell surface antigens.
10− 4
(4–6 colour)
10− 5
(8–10 colour)
1) Strong applicability (90–100%)
2) Fast, economical and efficient;
3) Built-in evaluation of sample quality;
4) Not affected by SHM and clonal evolution.
1) Need to be tested within 24-48 h;
2) Data analysis needs professional knowledge and technology;
3) Complex data visualization;
4) Cannot detect cytogenetic characteristics.
---Optimized version of MFC with higher sensitivity.
10−6 1) Nearly 100% applicability;
2) EuroFlow Consortium standardization;
3) Highly automated;
4) Based on the analysis of large numbers of cells;
1) Need to be tested within 24-48 h;
2) Cannot detect clonal evolution;
3) Complex data analysis.
---Identification of MM cells by amplifying MM-specific immunoglobulin gene rearrangement.
10−5 1) Wide range of applications (it can be used in almost all laboratories);
2) Fully standardized detection method and data interpretation standards;
3) No need to process bone marrow samples immediately;
1) The applicability is reduced to 42–75% when using universal primers;
2) The construction of a standard curve will consume a large number of limited bone marrow DNA samples;
3) May provide false negative results.
--- Identification of MM cells by sequencing the IGH/IGK/IGL loci.
10−6 1) No need to process samples immediately and no need for a standard curve;
2) Can capture almost all Ig gene rearrangements;
3) Uses consensus primers for clonality detection and subsequent MRD analysis;
4) Adaptive Biotechnologies
(Seattle, WA, US) standardization;
1) May be affected by SHM;
2) No sample built-in test;
3) It is time-consuming, labor-intensive, expensive, and cannot be universally used in clinics and laboratories;
4) Interpretation of results is really difficult, requiring high expertise.
--- Identification of MM cells by assessing tumor metabolic aberration
Spatial resolution limit of approximately 5 mm 1) Residual active clonal plasma cells can be detected in residual osteolytic lesions;
2) Accurately maps the sites of bone and extra-medullary disease;
3) It is complementary to cellular or molecular-based techniques;
1) May provide false positive results, for example: recent use of chemotherapy or/and growth factors to induce bone marrow reconstitution;
2) May provide false negative results, for example: lack of hexokinase enzyme or use of high-dose steroids;
3) Significant cost.
  1. Abbreviations: MRD measurable residual disease, MFC multiparameter flow cytometry, NGF next-generation flow cytometry, ASO-qPCR allele-specific oligonucleotide quantitative polymerase chain reaction, NGS next-generation sequencing, FDG-PET/CT positron emission tomography with computed tomography using 18F-deoxyglucose