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    A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study.

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    Author
    Rawstron, AC; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; ...
    Date
    2016-04
    Source Title
    Leukemia
    Publisher
    Springer Science and Business Media LLC
    University of Melbourne Author/s
    Westerman, David
    Affiliation
    Medicine and Radiology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Rawstron, A. C., Fazi, C., Agathangelidis, A., Villamor, N., Letestu, R., Nomdedeu, J., Palacio, C., Stehlikova, O., Kreuzer, K. -A., Liptrot, S., O'Brien, D., de Tute, R. M., Marinov, I., Hauwel, M., Spacek, M., Dobber, J., Kater, A. P., Gambell, P., Soosapilla, A. ,... Ghia, P. (2016). A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study.. Leukemia, 30 (4), pp.929-936. https://doi.org/10.1038/leu.2015.313.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257632
    DOI
    10.1038/leu.2015.313
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832072
    Abstract
    In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10(-5)). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10(-4)) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10(-6)). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.

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