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Next generation flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

AuthorsFlores-Montero, Juan; Sanoja, Luzalba; Paiva, Bruno; Puig, Noemi; García-Sánchez, O.; Böttcher, Sebastian; Velden, Vincent H. J. van der; Pérez-Morán, J.-J.; Vidriales, Maria Belén; García-Sanz, Ramón; Jiménez, Cristina ; González, Marcos ; Martínez-López, Joaquín; Corral-Mateos, A.; Grigore, Georgiana Emilia; Fluxá, Rafael; Pontes, R.; Caetano, J.; Sedek, Lukasz; Cañizo, María Consuelo del; Bladé, Joan; Lahuerta, Juan José; Aguilar, Carlos; Bárez, Abelardo; García-Mateo, Aránzazu; Labrador, Jorge; Leoz, P.; Aguilera-Sanz, C.; San Miguel, Jesús F. ; Mateos, Maria Victoria; Durie, B.; Dongen, J. J. M. van; Orfao, Alberto
Issue Date2017
PublisherNature Publishing Group
CitationLeukemia 31(10): 2094-2103 (2017)
AbstractFlow 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 ⩾107 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 version (URL)https://doi.org/10.1038/leu.2017.29
Identifiersdoi: 10.1038/leu.2017.29
e-issn: 1476-5551
issn: 0887-6924
Appears in Collections:(IBMCC) Artículos
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