A1 Refereed original research article in a scientific journal
Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1
Authors: T. Sacha, S. Schnittger, T. Touloumenidou, H. Valerhaugen, M. Mueller, F. Pane, L. Rai, C. Damm-Welk, S. Markovic, H. Pfeifer, G. Cazzaniga, V. H. J. van der Velden, J. M. Cayuela, B. Schäfer, O. Spinelli, S. Akiki, S. Avigad, I. Bendit, K. Borg, H. Cavé, L. Elia, S. C. Reshmi, G. Gerrard, S. Hayette, M. Hermanson, A. Juh, T. Jurcek, M. C. Chillón, C. Homburg, G. Martinelli, V. Kairisto, T. Lange, T. Lion, M. C. Mueller, F. Pane, L. Rai, C. Damm-Welk, T. Sacha, S. Schnittger, T. Touloumenidou, H. Valerhaugen, P. Vandenberghe, J. Zuna, H. Serve, E. Herrmann, S. Markovic, J. J. M. van Dongen, O. G. Ottmann
Publisher: Nature Publishing Group
Publication year: 2019
Journal: Leukemia
Journal name in source: Leukemia
Volume: 33
First page : 1910
Last page: 1922
DOI: https://doi.org/10.1038/s41375-019-0413-0
Minimal residual disease (MRD) is a powerful prognostic factor in acute
lymphoblastic leukemia (ALL) and is used for patient stratification and
treatment decisions, but its precise role in Philadelphia chromosome
positive ALL is less clear. This uncertainty results largely from
methodological differences relating to the use of real-time quantitative
PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD
analysis. We here describe the first results by the EURO-MRD consortium
on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in
Ph + ALL, designed to overcome the lack of standardisation of
laboratory procedures and data interpretation. Standardised use of EAC
primer/probe sets and of centrally prepared plasmid standards had the
greatest impact on reducing interlaboratory variability. In QC1 the
proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10−3 and 36/67 (53%) and 53/67 (79%) at 10−4BCR-ABL1/ABL1.
Standardized RNA extraction, cDNA synthesis and cycler platforms did
not improve results further, whereas stringent application of technical
criteria for assay quality and uniform criteria for data interpretation
and reporting were essential. We provide detailed laboratory
recommendations for the standardized MRD analysis in routine diagnostic
settings and in multicenter clinical trials for Ph + ALL.
