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Leukemia. 2016 Apr;30(4):929-36. doi: 10.1038/leu.2015.313. Epub 2015 Dec 7.

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 information

1
HMDS, St James's Institute of Oncology, Leeds, UK.
2
IRCCS San Raffaele Scientific Institute, Milano, Italy.
3
Hospital Clínic, IDIBAPS, Barcelona, Spain.
4
Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP), Bobigny, France.
5
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
6
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
7
Department of Internal Medicine-Hematology and Oncology, University Hospital Brno and CEITEC, Masaryk University, Brno, Czech Republic.
8
University Hospital, Cologne, Germany.
9
St James Hospital, Dublin, Ireland.
10
Institute of Hematology and Blood Transfusion, University Hospital Prague, Prague, Czech Republic.
11
University Hospital Geneva, Geneva, Switzerland.
12
General University Hospital, Prague, Czech Republic.
13
Department of Hematology, Academic Medical Centre, Amsterdam, Netherlands.
14
Peter MacCallum Cancer Centre, Melbourne, Australia.
15
Hematology and Flow Cytometry, Laverty Pathology, Sydney, Australia.
16
Ohio State University Medical Center, Columbus, OH, USA.
17
3rd Medical Department, Paracelsus Medical University, Salzburg, Austria.
18
Experimental and Clinical Cell Therapy Institute, Spinal Cord and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria.
19
Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.
20
Divisions of Hematology and Hematopathology, Mayo Clinic, Rochester, MN, USA.
21
MD Anderson Cancer Center, Houston, TX, USA.
22
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
23
Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
24
Un1iversity of Pittsburgh, Pittsburgh, PA, USA.
25
Department of Haematology, Royal North Shore Hospital, Sydney, Australia.
26
Adaptive Biotechnologies, Seattle, WA, USA.
27
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
28
Università Vita-Salute San Raffaele, Milan, Italy.

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.

PMID:
26639181
PMCID:
PMC4832072
DOI:
10.1038/leu.2015.313
[Indexed for MEDLINE]
Free PMC Article

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