Improved inter-lab precision after CML international scale adoption: a 15-year history of BCR::ABL1 proficiency...

Precise inter-laboratory quantitation of BCR::ABL1 RNA is critical for effective chronic myeloid leukemia (CML) disease management. Although standardized reporting on the International Scale (IS) was specifically developed to improve inter-laboratory reproducibility in BCR::ABL1 quantitation, the clinical impact of this reporting system has not been comprehensively assessed. We analyzed 15 years of BCR::ABL1 results (2009-2023) reported by over 200 clinical laboratories (6 annual samples; >5500 results) in a College of American Pathologists proficiency testing program. Inter-laboratory precision was evaluated by standard deviations (SD) for high, intermediate, and low-transcript samples. Early rapid IS adoption over 7 years (8% of labs in 2009; 86% by 2015) was correlated with a progressive decrease in inter-lab SDs of reported BCR::ABL1 results (high-sample r = -0.73, p = 0.004; intermediate-sample r = -0.71, p = 0.022; low-sample r = -0.84, p = 0.002). IS implementation exceeded 99% by 2019, as inter-lab SD's reached their nadir value (~0.2). No other assessed variable correlated with time-dependent improvement in inter-lab reproducibility, including reference gene selection (ABL1 versus others), RQ-PCR reagent selection, assay type (FDA-approved, commercial, or laboratory-developed), or practice setting. IS-based reporting is thus likely the principal driver of enhanced inter-laboratory precision in BCR::ABL1 quantitation, validating the real-world clinical relevance of adopting robust standardization in clinical molecular diagnostics.