Table 1.

Different techniques for measuring residual disease

TechniqueMethodsMaterialCutoffAdvantageDisadvantage
Multiparameter flow cytometry 
LAIP13  Identify and follow a specific LAIP BM 0.1%* LAIPs found in 90% of patients Misses clonal evolution 
Different from normal17  Identify leukemia cells in the empty spaces of normal BM flow plots BM Any MRD No need for a diagnostic sample Needs ample experience on regenerating normal BM 
LAIP-based different from normal48  Identify a LAIP at diagnosis but measure the whole panel to detect emerging cell populations BM 0.1% Usable for almost all patients Still needs experience on background LAIP levels 
Targeted molecular 
qPCR NPM1 BM/PB 2% copies per ABL copies Highly sensitive, rapid, standardizable Can be low-level present with no clinical consequences 
qPCR Translocations BM/PB 2% copies per ABL copies or 3-4 log reduction Highly sensitive, rapid, standardizable BM cannot be as measured frequently as PB 
Next-generation sequencing 
NGS24,25  NPM1 BM/PB 0.01%-0.1% Can be well standardized, reproducible, sensitive, flexible Not yet standardized, not comparable to qPCR yet, expensive, time consuming 
NGS15,23,26 FLT3/ITD BM/PB 0.01% Can be well standardized, reproducible, sensitive, flexible Expensive and clinical application needs to be validated 
TechniqueMethodsMaterialCutoffAdvantageDisadvantage
Multiparameter flow cytometry 
LAIP13  Identify and follow a specific LAIP BM 0.1%* LAIPs found in 90% of patients Misses clonal evolution 
Different from normal17  Identify leukemia cells in the empty spaces of normal BM flow plots BM Any MRD No need for a diagnostic sample Needs ample experience on regenerating normal BM 
LAIP-based different from normal48  Identify a LAIP at diagnosis but measure the whole panel to detect emerging cell populations BM 0.1% Usable for almost all patients Still needs experience on background LAIP levels 
Targeted molecular 
qPCR NPM1 BM/PB 2% copies per ABL copies Highly sensitive, rapid, standardizable Can be low-level present with no clinical consequences 
qPCR Translocations BM/PB 2% copies per ABL copies or 3-4 log reduction Highly sensitive, rapid, standardizable BM cannot be as measured frequently as PB 
Next-generation sequencing 
NGS24,25  NPM1 BM/PB 0.01%-0.1% Can be well standardized, reproducible, sensitive, flexible Not yet standardized, not comparable to qPCR yet, expensive, time consuming 
NGS15,23,26 FLT3/ITD BM/PB 0.01% Can be well standardized, reproducible, sensitive, flexible Expensive and clinical application needs to be validated 

qPCR, quantitative polymerase chain reaction.

*

LAIP cells/CD45-expressing cells.

RUNX1-RUNX1T1, CBFB-MYH11, PML-RARA, KMT2A-MLLT3, DEK-NUP214, BCR-ABL.

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