BCR-ABL1 (p210) Transcript Kinetics.

Area of Science:

• Molecular diagnostics
• Clinical assay monitoring
• Biostatistics

Background:

• Delta checks are valuable for monitoring clinical assays but underutilized in molecular testing.
• The biological kinetics of BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1) expression offer potential for delta check development.

Purpose of the Study:

• To assess if BCR-ABL1's natural rise and fall kinetics can support a delta check system.
• To establish a reliable delta check cutoff for BCR-ABL1 molecular testing.

Main Methods:

• Analysis of nine years of BCR-ABL1 p210 results from patients with at least three measurements.
• Plotting kinetics of percentage of international standard values against time, including median and percentile lines.
• Monte Carlo simulation using six months of data to test a proposed batch mix-up detection cutoff.

Main Results:

• Median BCR-ABL1 kinetics show a 1-log drop in 90 days; <5% exhibit >2-log drop, <2.5% show >3-log drop (extrapolated to 1 log/30 days).
• Monte Carlo simulation indicated the proposed cutoff could detect an average batch mix-up of 23 samples, despite variance.

Conclusions:

• A delta check trigger of >1 log drop in the percentage of international standard within 30 days is suggested.
• This delta check system can be a valuable tool for monitoring BCR-ABL1 molecular tests.