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

[EN]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 standardizati...

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Detalles Bibliográficos
Autores: Flores Montero, Juan Alejandro, Sanoja Flores, Luzalba, Paiva, Bruno, Puig Morón, Noemí, García Sánchez, Omar, Böttcher, Sebastian, van der Velden, VHJ, Pérez Morán, José, Vidriales Vicente, María Belén, García Sanz, Ramón, Jiménez, C., González Díaz, Marcos, Martínez-López, J., Corral-Mateos, A., Grigori, G.E., Fluxá, R., Pontes, R., Caetano, J., Sedek, L., Cañizo Fernández-Roldán, María Consuelo del, Bladé, Joan, Huerta, Juan José la, Aguilar, Carlos, Bárez, Abelardo, García-Mateo, A., Labrador Gómez, Jorge, Leoz, P., Aguilera-Sanz, C., San Miguel, Jesús F, Mateos Manteca, María Victoria, Durie, Brian, van Dongen, Jacques J. M., Orfao de Matos Correia e Vale, José Alberto
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/136897
Acceso en línea:http://hdl.handle.net/10366/136897
Access Level:acceso abierto
Palabra clave:Oncology
Next generation flow
Multiple myeloma
Minimal residual disease
Descripción
Sumario:[EN]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.

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