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Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma
Autores: Flores-Montero, J.; Sanoja-Flores, L.; Paiva, Bruno; Puig, N.; García-Sánchez, O.; Bottcher, S.; van der Velden, V. H. J.; Pérez-Moran, J. J.; Vidriales, M. B.; García-Sanz, R.; Jiménez, C.; González, M.; Martínez-López, J.; Corral-Mateos, A.; Grigore, G. E.; Fluxa, R.; Pontes, R.; Caetano, J.; Sedek, L.; del Canizo, M. C.; Blade, J.; Lahuerta, J. J.; Aguilar, C.; Barez, A.; García-Mateo, A.; Labrador, J.; Leoz, P.; Aguilera-Sanz, C.; San Miguel Izquierdo, Jesús; Mateos, M. V.; Durie, B.; van Dongen, J. J. M.; Orfao, A.
Título de la revista: LEUKEMIA
ISSN: 0887-6924
Volumen: 31
Número: 10
Páginas: 2094 - 2103
Fecha de publicación: 2017
Lugar: WOS
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. 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.