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., 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. and 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). S. 929 - 937. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5551

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rawstron, A. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fazi, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agathangelidis, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villamor, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Letestu, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nomdedeu, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palacio, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stehlikova, O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuzer, K-AUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liptrot, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Brien, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Tute, R. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marinov, I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauwel, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spacek, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dobber, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kater, A. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gambell, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soosapilla, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lozanski, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brachtl, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lin, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boysen, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hanson, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jorgensen, J. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stetler-Stevenson, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yuan, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broome, H. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rassenti, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Craig, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delgado, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moreno, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bosch, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egle, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doubek, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pospisilova, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mulligan, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westerman, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanders, C. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Emerson, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robins, H. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirsch, I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shanafelt, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pettitt, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kipps, T. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wierda, W. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cymbalista, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillmen, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montserrat, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghia, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-279834
DOI: 10.1038/leu.2015.313
Journal or Publication Title: Leukemia
Volume: 30
Number: 4
Page Range: S. 929 - 937
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5551
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ASSAY; QUANTIFICATION; RITUXIMAB; SURVIVAL; THERAPY; ERADICATION; EXPRESSION; GUIDELINES; DIAGNOSIS; TRIALMultiple languages
Oncology; HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27983

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