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

A. C. Rawstron, C. Fazi, A. Agathangelidis, N. Villamor, R. Letestu, J. Nomdedeu, C. Palacio, O. Stehlikova, K. A. Kreuzer, S. Liptrot, D. O'Brien, R. M. de Tute, I. Marinov, M. Hauwel, M. Spacek, J. Dobber, A. P. Kater, P. Gambell, A. Soosapilla, G. LozanskiG. Brachtl, K. Lin, J. Boysen, C. Hanson, J. L. Jorgensen, M. Stetler-Stevenson, C. Yuan, H. E. Broome, L. Rassenti, F. Craig, J. Delgado, C. Moreno, F. Bosch, A. Egle, M. Doubek, S. Pospisilova, S. Mulligan, D. Westerman, C. M. Sanders, R. Emerson, H. S. Robins, I. Kirsch, T. Shanafelt, A. Pettitt, T. J. Kipps, W. G. Wierda, F. Cymbalista, M. Hallek, P. Hillmen, E. Montserrat, P. Ghia

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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.Leukemia advance online publication, 29 January 2016; doi:10.1038/leu.2015.313.

Original languageEnglish
JournalLeukemia
DOIs
Publication statusAccepted/In press - Dec 7 2015

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Residual Neoplasm
B-Cell Chronic Lymphocytic Leukemia
Flow Cytometry
Research
Limit of Detection
Publications
Leukemia
Guidelines
Technology
Education
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

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. / 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.; Ghia, P.

In: Leukemia, 07.12.2015.

Research output: Contribution to journalArticle

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, HS, Kirsch, I, Shanafelt, T, Pettitt, A, Kipps, TJ, Wierda, WG, Cymbalista, F, Hallek, M, Hillmen, P, Montserrat, E & Ghia, P 2015, '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. https://doi.org/10.1038/leu.2015.313
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. ; Ghia, P. / 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. In: Leukemia. 2015.
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title = "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",
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.Leukemia advance online publication, 29 January 2016; doi:10.1038/leu.2015.313.",
author = "Rawstron, {A. C.} and C. Fazi and A. Agathangelidis and N. Villamor and R. Letestu and J. Nomdedeu and C. Palacio and O. Stehlikova and Kreuzer, {K. A.} and S. Liptrot and D. O'Brien and {de Tute}, {R. M.} and I. Marinov and M. Hauwel and M. Spacek and J. Dobber and Kater, {A. P.} and P. Gambell and A. Soosapilla and G. Lozanski and G. Brachtl and K. Lin and J. Boysen and C. Hanson and Jorgensen, {J. L.} and M. Stetler-Stevenson and C. Yuan and Broome, {H. E.} and L. Rassenti and F. Craig and J. Delgado and C. Moreno and F. Bosch and A. Egle and M. Doubek and S. Pospisilova and S. Mulligan and D. Westerman and Sanders, {C. M.} and R. Emerson and Robins, {H. S.} and I. Kirsch and T. Shanafelt and A. Pettitt and Kipps, {T. J.} and Wierda, {W. G.} and F. Cymbalista and M. Hallek and P. Hillmen and E. Montserrat and P. Ghia",
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T1 - A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia

T2 - an European Research Initiative on CLL study

AU - Rawstron, A. C.

AU - Fazi, C.

AU - Agathangelidis, A.

AU - Villamor, N.

AU - Letestu, R.

AU - Nomdedeu, J.

AU - Palacio, C.

AU - Stehlikova, O.

AU - Kreuzer, K. A.

AU - Liptrot, S.

AU - O'Brien, D.

AU - de Tute, R. M.

AU - Marinov, I.

AU - Hauwel, M.

AU - Spacek, M.

AU - Dobber, J.

AU - Kater, A. P.

AU - Gambell, P.

AU - Soosapilla, A.

AU - Lozanski, G.

AU - Brachtl, G.

AU - Lin, K.

AU - Boysen, J.

AU - Hanson, C.

AU - Jorgensen, J. L.

AU - Stetler-Stevenson, M.

AU - Yuan, C.

AU - Broome, H. E.

AU - Rassenti, L.

AU - Craig, F.

AU - Delgado, J.

AU - Moreno, C.

AU - Bosch, F.

AU - Egle, A.

AU - Doubek, M.

AU - Pospisilova, S.

AU - Mulligan, S.

AU - Westerman, D.

AU - Sanders, C. M.

AU - Emerson, R.

AU - Robins, H. S.

AU - Kirsch, I.

AU - Shanafelt, T.

AU - Pettitt, A.

AU - Kipps, T. J.

AU - Wierda, W. G.

AU - Cymbalista, F.

AU - Hallek, M.

AU - Hillmen, P.

AU - Montserrat, E.

AU - Ghia, P.

PY - 2015/12/7

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N2 - 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.Leukemia advance online publication, 29 January 2016; doi:10.1038/leu.2015.313.

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