Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Leukemia, 2017-10, Vol.31 (10), p.2094-2103

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 7 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.