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

被引：483

作者：

Flores-Montero, J. ^{[1
,2
,3
]}

Sanoja-Flores, L. ^{[1
,2
,3
]}

Paiva, B. ^{[4
,5
]}

Puig, N. ^{[6
,7
]}

Garcia-Sanchez, O. ^{[6
,7
]}

Boettcher, S. ^{[8
]}

van der Velden, V. H. J. ^{[9
]}

Perez-Moran, J-J ^{[6
,7
]}

Vidriales, M-B ^{[6
,7
]}

Garcia-Sanz, R. ^{[6
,7
]}

Jimenez, C. ^{[6
,7
]}

Gonzalez, M. ^{[6
,7
]}

Martinez-Lopez, J. ^{[10
]}

Corral-Mateos, A. ^{[1
,2
,3
]}

Grigore, G-E ^{[11
]}

Fluxa, R. ^{[11
]}

Pontes, R. ^{[12
,13
]}

Caetano, J. ^{[14
]}

Sedek, L. ^{[15
]}

del Canizo, M-C ^{[6
,7
]}

Blade, J. ^{[16
]}

Lahuerta, J-J ^{[10
]}

Aguilar, C. ^{[17
]}

Barez, A. ^{[18
]}

Garcia-Mateo, A. ^{[19
]}

Labrador, J. ^{[20
]}

Leoz, P. ^{[1
,2
,3
]}

Aguilera-Sanz, C. ^{[21
]}

San-Miguel, J. ^{[4
,5
]}

Mateos, M-V ^{[6
,7
]}

Durie, B. ^{[22
]}

van Dongen, J. J. M. ^{[23
]}

Orfao, A. ^{[1
,2
,3
]}

机构：

[1] USAL, IBSAL, CSIC, Canc Res Ctr,IBMCC, Salamanca, Spain

[2] Univ Salamanca, Cytometry Serv NUCLEUS, Salamanca, Spain

[3] Univ Salamanca, Dept Med, USAL, Salamanca, Spain

[4] Clin Univ Navarra, Pamplona, Spain

[5] UNAV, IDISNA, Appl Med Res Ctr CIMA, Pamplona, Spain

[6] Univ Hosp Salamanca, IBSAL, Dept Hematol, Salamanca, Spain

[7] USAL, CSIC, HUSAL, IBMCC, Salamanca, Spain

[8] Univ Hosp Schleswig Holstein, Dept Med 2, UNIKIEL, Campus Kiel, Kiel, Germany

[9] Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, EMC, Rotterdam, Netherlands

[10] Hosp 12 Octubre, Dept Hematol, Madrid, Spain

[11] Cytognos SL, Salamanca, Spain

[12] Univ Fed Rio de Janeiro, Fac Med, Rio De Janeiro, Brazil

[13] Inst Pediat & Childhood Care, Rio De Janeiro, Brazil

[14] Portuguese Inst Oncol, Dept Hematol, IPOLFG, Lisbon, Portugal

[15] Med Univ Silesia, Dept Pediat Hematol & Oncol, Zabrze, Poland

[16] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain

[17] Hosp Gen Santa Barbara, Dept Hematol, Soria, Spain

[18] Complejo Asistencial Avila, Dept Hematol, Avila, Spain

[19] Complejo Asistencial Segovia, Dept Hematol, Segovia, Spain

[20] Hosp Univ Burgos, Hematol Dept, Burgos, Spain

[21] Hosp El Bierzo, Dept Hematol, Ponferrada, Spain

[22] Cedars Sinai Samuel Oschin Canc Ctr, Los Angeles, CA USA

[23] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands

来源：

LEUKEMIA | 2017年 / 31卷 / 10期

关键词：

STEM-CELL TRANSPLANTATION; TIME QUANTITATIVE PCR; ASO RQ-PCR; PLASMA-CELLS; CONSENSUS GUIDELINES; INITIAL TREATMENT; COMPLETE RESPONSE; CYTOMETRY; IMMUNOGLOBULIN; CRITERIA;

D O I：

10.1038/leu.2017.29

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2094 / 2103

页数：10

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