From: Minimal residual disease in multiple myeloma: current status
Techniques | Sensitivity | Advantages | Disadvantages |
---|---|---|---|
MFC --- 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. |
NGF ---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. |
ASO-qPCR ---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. |
NGS --- 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. |
FDG-PET/CT --- 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. |