Table 2.

Comparison of different bone marrow MRD techniques

CharacteristicFlow cytometryImmunoglobulin NGS
Applicability Nearly 100% ≥90% 
Diagnostic sample Ideally, sample with myeloma present, although abnormal plasma cells can be identified in any sample by their distinct immunophenotypic pattern vs normal plasma cells Sample with myeloma present (e.g., presentation) required for identification of the dominant clonotype 
Sample requirements 2-5 million cells 1 million cells 
Sample processing Requires fresh sample; assessed within 24-48 h Can use both fresh and stored samples 
Standardization Methodology varies between laboratories. Some attempts at standardization (e.g., EuroFlow) Standardized methodology available from commercial companies. Academic methodologies also available 
Quantitative Yes Yes 
Sensitivity 1 in 104 to 1 in 106 1 in 105 to 1 in 106 
Turnaround and complexity Hours. Requires skilled flow cytometrist. Automated software available 1 wk. Bioinformatic analysis available 
Clonal evolution Considers all clones with similar phenotype but evolving clone with change in phenotype may not be evaluable Can take into account all minor clones with infrequent occurrence 
Availability Many laboratories with 4 color; 8 or more colors restricted to more specialized centers One company commercially and a number of academic platforms 
CharacteristicFlow cytometryImmunoglobulin NGS
Applicability Nearly 100% ≥90% 
Diagnostic sample Ideally, sample with myeloma present, although abnormal plasma cells can be identified in any sample by their distinct immunophenotypic pattern vs normal plasma cells Sample with myeloma present (e.g., presentation) required for identification of the dominant clonotype 
Sample requirements 2-5 million cells 1 million cells 
Sample processing Requires fresh sample; assessed within 24-48 h Can use both fresh and stored samples 
Standardization Methodology varies between laboratories. Some attempts at standardization (e.g., EuroFlow) Standardized methodology available from commercial companies. Academic methodologies also available 
Quantitative Yes Yes 
Sensitivity 1 in 104 to 1 in 106 1 in 105 to 1 in 106 
Turnaround and complexity Hours. Requires skilled flow cytometrist. Automated software available 1 wk. Bioinformatic analysis available 
Clonal evolution Considers all clones with similar phenotype but evolving clone with change in phenotype may not be evaluable Can take into account all minor clones with infrequent occurrence 
Availability Many laboratories with 4 color; 8 or more colors restricted to more specialized centers One company commercially and a number of academic platforms