Portal de Periódicos da CAPES

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

2015; Springer Nature; Volume: 30; Issue: 4 Linguagem: Inglês

10.1038/leu.2015.313

1476-5551

Andy C. Rawstron, Claudia Fazi, Andreas Agathangelidis, Neus Villamor, Rémi Letestu, Josep Nomdedéu, Carlos Palacio, Olga Stehlíková, K-A Kreuzer, Stuart Liptrot, David O’Brien, Ruth M. de Tute, Iuri Marinov, Mathieu Hauwel, Martin Špaček, Johan A. Dobber, Arnon P. Kater, Peter Gambell, Asha Soosapilla, Gerard Lozanski, Gabriele Brachtl, Ke Lin, Justin C. Boysen, Curtis A. Hanson, Jeffrey L. Jorgensen, Maryalice Stetler‐Stevenson, Constance M. Yuan, H. Elizabeth Broome, Laura Z. Rassenti, Fiona E. Craig, Julio Delgado, Carol Moreno, Francesc Bosch, Alexander Egle, Michael Doubek, Šárka Posp̂íšilová, Stephen P. Mulligan, David Westerman, Catherine Sanders, Ryan Emerson, Harlan Robins, Ilan Kirsch, Tait D. Shanafelt, Andrew R. Pettitt, Thomas J. Kipps, William G. Wierda, Florence Cymbalista, Michael Hallek, Peter Hillmen, Emili Montserrat, Paolo Ghia,

Lymphoma Diagnosis and Treatment

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.