External quality assessment of BCR-ABL1 quantification in chronic myeloid leukemia: a pilot interlaboratory study from Russia

BCR-ABL1 is a chimeric oncogene underlying chronic myeloid leukemia (CML) and serves as a key marker for monitoring minimal residual disease. Quantitative RT-qPCR analysis of BCR-ABL1 transcripts enables assessment of molecular response depth and timely detection of treatment failure or resistance. In international practice, the introduction of the International Scale (IS), along with method standardization, has significantly improved the comparability of results between laboratories. Participation in external quality assessment (EQA) programs is a mandatory accreditation requirement in countries with established CML monitoring systems, allowing laboratories to evaluate analytical accuracy and to adjust protocols when deviations are detected. Until recently, Russia lacked both standardized IS calibration and a national EQA program for BCR-ABL1 testing, which hindered the assessment of interlaboratory precision. This pilot study represents the first interlaboratory comparison of quantitative BCR-ABL1 measurement in the Russian Federation. Two panels of lyophilized control samples (five levels each, from M1 to M4.5) were distributed and analyzed by 14 laboratories (15 datasets) using their routine protocols without IS conversion. Interlaboratory variability was high: the overall coefficient of variation ranged from approximately 40 percent to 50 percent, with individual laboratory results at the high level (about 10 percent) varying from 3 percent to 27 percent. Most laboratories results were within plus/minus 3 standard deviations of the consensus median, but two laboratories showed consistent overestimation (bias about +3.8 percentage points) or underestimation (bias about -1.7 percentage points), leading to multi-fold errors at level M1. These findings highlight the urgent need to implement IS calibration and to establish a national EQA program for BCR-ABL1 testing in Russia to improve result comparability. Adoption of these measures will help align molecular monitoring of CML in Russia with international standards and strengthen clinician confidence in laboratory testing