A QA Program for MRD Testing Demonstrates That Systematic Education Can Reduce Discordance Among Experienced Interpreters

Abstract

Despite the provision of the COG standardized analysis protocol, even experienced laboratories require an educational component for B-ALL MRD analysis by FCM. Recognition of hematogones remains challenging for some labs when using the COG protocol. The results from this study suggest that dissemination of MRD testing to other North American laboratories as part of routine clinical management of B-ALL is possible but requires additional educational components to complement standardized methodology. © 2017 International Clinical Cytometry Society.

Applications of Flow Cytometric Immunophenotyping in the Diagnosis and Posttreatment Monitoring of B and T Lymphoblastic Leukemia/Lymphoma

“…Residual leukemia is recognized by visual inspection by a trained observer of dot plots for all fluorochrome combinations, gated on CD19+ events, to identify a cluster of events that is not artifact and different in immunophenotype from any stage of normal or regenerating B cell maturation. Training for those evaluating MRD flow cytometric data is a critical source of variability, as has been convincingly shown for the COG assay . A third reagent combination contains a DNA/RNA binding dye (Syto16) that provides a nucleated cell denominator used for enumeration in conjunction with CD45.…”

Reproducibility of Flow Cytometry Through Standardization: Opportunities and Challenges

“…The Children's Oncology Group (COG) study developed a unified minimal residual disease detection approach (44) deployed in two centers for the COG study AALL0232 that used the same antibody panel, although on different cytometers, and demonstrated excellent interlaboratory enumeration correlation (31). Recently, COG developed a QA scheme and educational program for BCP-ALL MRD (45).…”

Issue Highlights—March 2018

“…EQA exercises are being more and more split into “wet” exercises, with the distribution of stabilized samples to evaluate the entire cell phenotyping process and “dry” exercises, in which datafiles of multicolor experiments are distributed to focus on the operators' ability to manage complex gating syntax and data interpretation. The paper by Keeney et al shows that despite a thorough training, in B‐ALL Minimal Residual Disease (MRD) analysis also experienced centers may initially incur a result variability as high as 26% solely due to gate placement and data interpretation problems. By repeated training and exercise rounds this variability luckily plummets to a more acceptable 9%.…”