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Letters to the Editor
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Figure 2. Concordance of minimal residual disease levels, monoclonal plasma cell immunophenotype, and polyclonal plasma cell levels between European Myeloma Network multiparameter flow cytometry laboratories. Minimal residual disease (MRD) levels were highly concordant between laboratories, irrespec- tive of disease burden, disease stage, treatment status, sample type and quality assurance (QA) round. (A) A total of 10/20 (50%) samples were MRD-positive, which could be confirmed by all laboratories in 9/10 (90%) cases, using a cutoff of ≥20 monoclonal plasma cells (mPC) for MRD positivity. MRD-negative results were concordant between laboratories in 10/10 (100%) cases. In MRD-negative assays, a limit of detection <0.001% was reached in 11/16 (69%) samples in QA rounds 1-2, versus 14/18 (78%) of samples in QA rounds 3-4. In contrast, a limit of quantification <0.001% was reached in 4/16 (25%) of MRD-negative assays in QA rounds 1-2, versus 9/18 (50%) of MRD negative assays in QA rounds 3-4. MRD-positive samples showed a high degree of concordance between laboratories at every level of (residual) disease, ranging from 0.001-0.01% to 1-10%. (B) Qualitative expression of essential markers for mPC gating (i.e., CD38, CD138, CD45, CD19, CD56, CyIgK, CyIgL) showed a high degree of concordance between laboratories, whereas other informative markers (i.e., CD27, CD117, CD81) showed greater variability, indicating that strict uniformization of protocols is essential to ensure reproducibility of immunophenotype data. (C) The level of polyclonal plasma cells (pPC) is commonly used as a surrogate marker for bone marrow sample quality and generally showed a good concordance between laboratories. Nevertheless, the concordance of pPC levels was inferior to that of mPC levels, suggesting that pPC levels are more susceptible than mPC levels to interlaboratory variations in sample processing and data analysis strategies. ID: identifier; IP: immunophenotype; LOD: limit of detection = 20/total number of leukocytes; LOQ: limit of quantitation = 50/total number of leukocytes;15 MRD: minimal residual disease. NGF: next-generation flow; QA: quality assurance.
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