Table 2 Harmonized methods for residual disease detection using ERIC-harmonized approaches

From: A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study

Application

Assay

Advantages

Disadvantages

Trials aiming for disease control rather than eradication, e.g. continuous BCR pathway inhibition

Clonality assessment

•Relatively inexpensive and simple

•Requires capacity to reflex to full MRD assay if CLL cells <1.0% and/or B cells polyclonal

Trials focusing on achieving <0.010% MRD, i.e. with broadly similar responses rates to FCR,

4-color

4-tube

•Published outcome data.

•Does not require pretreatment phenotype for typical CLL

•Limit of detection >0.0050%

•More material required to achieve higher detection limits

requiring an MRD assessment that is published and has been used in previous clinical trials

6-color

2-tube

•Harmonized with 4-color assay

•Does not require pretreatment phenotype for typical CLL

•Intermediate LOD/LOQ

•Intermediate amount of material required to achieve higher detection limits

Trials aiming for significant improvements in disease depletion compared with FCR

6-color core panel for ⩾6-color assays

1-tube

•Permits flexibility for individual laboratory requirements

•LOD 0.0010% (10-5), LOQ 0.0025%

•Allows simultaneous analysis of additional markers

•Knowledge of pretreatment phenotype preferable

 

High throughput sequencing

•LOD 0.00010% (10-6)

•Objective analysis, does not necessarily require expert interpretation

•Further development work on standardization of the quantification

  1. Abbreviations: LOD, limit of detection; LOQ, limit of quantification.
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