1. 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
- Author
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Rawstron, AC, Fazi, C, Agathangelidis, A, Villamor, N, Letestu, R, Nomdedeu, J, Palacio, C, Stehlikova, O, Kreuzer, K-A, Liptrot, S, O'Brien, D, de Tute, RM, Marinov, I, Hauwel, M, Spacek, M, Dobber, J, Kater, AP, Gambell, P, Soosapilla, A, Lozanski, G, Brachtl, G, Lin, K, Boysen, J, Hanson, C, Jorgensen, JL, Stetler-Stevenson, M, Yuan, C, Broome, HE, Rassenti, L, Craig, F, Delgado, J, Moreno, C, Bosch, F, Egle, A, Doubek, M, Pospisilova, S, Mulligan, S, Westerman, D, Sanders, CM, Emerson, R, Robins, HS, Kirsch, I, Shanafelt, T, Pettitt, A, Kipps, TJ, Wierda, WG, Cymbalista, F, Hallek, M, Hillmen, P, Montserrat, E, Ghia, P, CLL, ERIC European Res Initiative, Rawstron, Ac, Fazi, C, Agathangelidis, A, Villamor, N, Letestu, R, Nomdedeu, J, Palacio, C, Stehlikova, O, Kreuzer, Ka, Liptrot, S, O'Brien, D, de Tute, Rm, Marinov, I, Hauwel, M, Spacek, M, Dobber, J, Kater, Ap, Gambell, P, Soosapilla, A, Lozanski, G, Brachtl, G, Lin, K, Boysen, J, Hanson, C, Jorgensen, Jl, Stetler Stevenson, M, Yuan, C, Broome, He, Rassenti, L, Craig, F, Delgado, J, Moreno, C, Bosch, F, Egle, A, Doubek, M, Pospisilova, S, Mulligan, S, Westerman, D, Sanders, Cm, Emerson, R, Robins, H, Kirsch, I, Shanafelt, T, Pettitt, A, Kipps, Tj, Wierda, Wg, Cymbalista, F, Hallek, M, Hillmen, P, Montserrat, E, Ghia, PAOLO PROSPERO, AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, and Clinical Haematology
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,Neoplasm, Residual ,Lymphoma ,Chronic lymphocytic leukemia ,0302 clinical medicine ,Immunophenotyping ,immune system diseases ,hemic and lymphatic diseases ,Chronic ,Cancer ,CD20 ,Hematology ,Leukemia ,biology ,High-Throughput Nucleotide Sequencing ,Prognosis ,Flow Cytometry ,Combined Modality Therapy ,Lymphocytic ,3. Good health ,CD ,Europe ,030220 oncology & carcinogenesis ,Residual ,Original Article ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,03 medical and health sciences ,Young Adult ,Rare Diseases ,Antigens, CD ,Internal medicine ,medicine ,Humans ,Antigens ,Neoplasm Staging ,business.industry ,B-Cell ,CD79B ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Minimal residual disease ,Orphan Drug ,030104 developmental biology ,biology.protein ,Neoplasm ,CD5 ,business ,Follow-Up Studies - 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.
- Published
- 2016