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Minimal Residual Disease

Development of standardized approaches to reporting of minimal residual disease data using a reporting software package designed within the European LeukemiaNet

Abstract

Quantitative PCR (qPCR) for detection of fusion transcripts and overexpressed genes is a promising tool for following minimal residual disease (MRD) in patients with hematological malignancies. Its widespread clinical use has to some extent been hampered by differences in data analysis and presentation that complicate multicenter clinical trials. To address these issues, we designed a highly flexible MRD-reporting software program, in which data from various qPCR platforms can be imported, processed, and presented in a uniform manner to generate intuitively understandable reports. The software was tested in a two-step quality control (QC) study; the first step involved eight centers, whose previous experience with the software ranged from none to extensive. The participants received cDNA from consecutive samples from a BCR-ABL+ chronic myeloid leukemia (CML) patient and an acute myeloid leukemia (AML) patient with both CBFβ-MYH11 and WT1 target genes, they conducted qPCR on their respective hardware platforms and generated a series of reports with pre-defined features. In step two, five centers used the software to report BCR-ABL+ MRD in a harmonized manner, applying their recently obtained CML international scale conversion factors. The QC study demonstrated that this MRD-reporting software is suitable for efficient handling of qPCR data, generation of MRD reports and harmonization of MRD data.

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Acknowledgements

We wish to thank Nicolas Maroc from Ipsogen for kindly providing reagents for the QC Study and Karin Brændstrup, Lone Siig Mikkelsen and Bodil Lind Andersen for excellent technical assistance at the Aarhus laboratory. We also thank the members of the ELN WP12 who have contributed to the development of our software. We thank Hans Beier Ommen for valuable input throughout the study and Tor Foss Mortensen, the owner of Langtved Data, for a fruitful cooperation. Thanks to Robert Schou Pedersen, Stanislaw Pulczynski and Jesper Stentoft for collecting samples for the QC II Study. DG is grateful to Leukaemia and Lymphoma Research of Great Britain and the National Institute for Health Research for support for MRD studies within the UK national AML trials. Supported by a grant from the European LeukemiaNet to DG, and by grants to PH from the Danish Cancer Society, the Danish Medical Research Council, the Karen Elise Jensen Foundation, and the John & Birthe Meyer Foundation.

Author contributions

PH and DG took the initiative to generate the software. MØ and CGN participated to an equal extent in its initial development in conjunction with JKL. MØ and JKL were responsible for the further development of the program, while CGN and LG were responsible for all aspects of the QC study. SS and KT were involved in testing and evaluation of preliminary software versions, all other authors were participants in the QC study by performing qPCR on shipped samples and by submitting report sheets as detailed. PH, MØ and CGN wrote the first draft, which was reviewed by DG before it was sent to the remaining authors. All authors have approved of the final version of the MS.

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European LeukemiaNet: http://www.leukemia-net.org

Langtved Data: http://www.Langtved.dk

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Correspondence to P Hokland.

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Competing interests

JKL is an employee at Langtved Data, who received financial support from the European LeukemiaNet (WP12) to develop the program. None of the other authors have financial relations to the company. All ELN WP12 members have the right to use the program. The program is owned by Langtved Data Ltd, which has made an agreement with ELN to further develop it and to commercialize it to non-ELN participants.

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Supplementary Information accompanies the paper on the Leukemia website

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Østergaard, M., Nyvold, C., Jovanovic, J. et al. Development of standardized approaches to reporting of minimal residual disease data using a reporting software package designed within the European LeukemiaNet. Leukemia 25, 1168–1173 (2011). https://doi.org/10.1038/leu.2011.69

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