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.
Authors
Rawstron, A CFazi, 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
Lozanski, G
Brachtl, G
Lin, K
Boysen, J
Hanson, C
Jorgensen, J L
Stetler-Stevenson, M
Yuan, C
Broome, H E
Rassenti, L
Craig, F
Delgado, J
Moreno, C
Bosch, F
Egle, A
Doubek, M
Pospisilova, S
Mulligan, S
Westerman, D
Sanders, C M
Emerson, R
Robins, H S
Kirsch, I
Shanafelt, T
Pettitt, A
Kipps, T J
Wierda, W G
Cymbalista, F
Hallek, M
Hillmen, P
Montserrat, E
Ghia, P
Issue Date
2016-04Keywords
LEUKAEMIAMeSH
AdolescentAdult
Antigens, CD
Combined Modality Therapy
Europe
Female
Flow Cytometry
Follow-Up Studies
High-Throughput Nucleotide Sequencing
Humans
Immunophenotyping
Leukemia, Lymphocytic, Chronic, B-Cell
Male
Neoplasm Staging
Neoplasm, Residual
Prognosis
Young Adult
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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. 2016, 30 (4):929-36 LeukemiaJournal
LeukemiaDOI
10.1038/leu.2015.313PubMed ID
26639181Abstract
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.Item Type
ArticleLanguage
enISSN
1476-5551ae974a485f413a2113503eed53cd6c53
10.1038/leu.2015.313
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