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Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

Leukemia, 2017-10, Vol.31 (10), p.2094-2103 [Peer Reviewed Journal]

COPYRIGHT 2017 Nature Publishing Group ;COPYRIGHT 2017 Nature Publishing Group ;Copyright Nature Publishing Group Oct 2017 ;Copyright © 2017 The Author(s) 2017 The Author(s) ;ISSN: 0887-6924 ;EISSN: 1476-5551 ;DOI: 10.1038/leu.2017.29 ;PMID: 28104919

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Title:
Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma
Author: Flores-Montero, J ; Sanoja-Flores, L ; Paiva, B ; Puig, N ; García-Sánchez, O ; Böttcher, S ; van der Velden, V H J ; Pérez-Morán, J-J ; Vidriales, M-B ; García-Sanz, R ; Jimenez, C ; González, M ; Martínez-López, J ; Corral-Mateos, A ; Grigore, G-E ; Fluxá, R ; Pontes, R ; Caetano, J ; Sedek, L ; Del Cañizo, M-C ; Bladé, J ; Lahuerta, J-J ; Aguilar, C ; Bárez, A ; García-Mateo, A ; Labrador, J ; Leoz, P ; Aguilera-Sanz, C ; San-Miguel, J ; Mateos, M-V ; Durie, B ; van Dongen, J J M ; Orfao, A
Subjects: Adult ; Aged ; Aged, 80 and over ; Antibody Specificity ; Bone marrow ; Care and treatment ; Cell Count ; Color ; Cytometry ; Development and progression ; Equipment Design ; Evaluation ; Female ; Flow ; Flow cytometry ; Flow Cytometry - instrumentation ; Flow Cytometry - methods ; Gating ; Health status indicators ; Humans ; Immunophenotyping - instrumentation ; Immunophenotyping - methods ; Lysis ; Male ; Middle Aged ; Minimal residual disease ; Multiple myeloma ; Multiple Myeloma - diagnosis ; Multiple Myeloma - drug therapy ; Multiple Myeloma - pathology ; Neoplasm, Residual ; Nerve growth factor ; Original ; Patients ; Plasma Cells - pathology ; Redesign ; Sensitivity ; Sensitivity and Specificity ; Software ; Software development tools ; Specimen Handling ; Standardization ; Survival ; Treatment Outcome
Is Part Of: Leukemia, 2017-10, Vol.31 (10), p.2094-2103
Description: Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0887-6924
EISSN: 1476-5551
DOI: 10.1038/leu.2017.29
PMID: 28104919
Source: MEDLINE
ProQuest Central

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Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

COPYRIGHT 2017 Nature Publishing Group ;COPYRIGHT 2017 Nature Publishing Group ;Copyright Nature Publishing Group Oct 2017 ;Copyright © 2017 The Author(s) 2017 The Author(s) ;ISSN: 0887-6924 ;EISSN: 1476-5551 ;DOI: 10.1038/leu.2017.29 ;PMID: 28104919

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