1. Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis
- Author
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Alfonso García de Coca, Alberto Orfao, Albert Pérez-Montaña, Mercedes Gironella, María José Casanova, Noemi Puig, Valentin Cabañas, Isabel Krsnik, Quentin Lecrevisse, Jose-Enrique de la Puerta, Bruno Paiva, Juana Merino, Felipe Prosper, Enrique M. Ocio, Juan José Lahuerta, Cristina Moreno, Javier Verde, Felipe de Arriba, Jesús F. San Miguel, Maria-Teresa Cedena, Ramón Lecumberri, Dolores Gómez Toboso, Maria Victoria Mateos, Leire Burgos, Jorge Labrador, Luis Palomera, María Belén Vidriales, Joaquin Martinez-Lopez, José de Jesús Pérez, Javier de la Rubia, Maria-Esther Gonzalez, Marta Lasa, Albert Oriol, Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, International Myeloma Foundation, and European Research Council
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,Identification ,Plasma-cells ,Myeloma ,Translocation (11/14) ,0302 clinical medicine ,Immunophenotyping ,Bone Marrow ,Mass Screening ,Immunoglobulin Light-chain Amyloidosis ,Multiple myeloma ,Aged, 80 and over ,Amyloidosis ,Diagnosed AL amyloidosis ,Hematology ,Middle Aged ,Flow Cytometry ,Immunoglobulin Isotypes ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,CD43 expression ,Female ,Adult ,medicine.medical_specialty ,Risk Assessment ,Differential-diagnosis ,Clonal Evolution ,Multiple-myeloma ,03 medical and health sciences ,Internal medicine ,medicine ,AL amyloidosis ,Humans ,Adverse prognostic-factor ,Mass screening ,Aged ,Neoplasm Staging ,Haematological cancer ,business.industry ,Minimal residual disease ,Translational research ,medicine.disease ,Staging system ,030104 developmental biology ,Bone marrow ,Differential diagnosis ,business ,Biomarkers - Abstract
Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤.03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P, This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00400 and CB16/12/00489), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI13/02196), Asociación Española Contra el Cáncer (GCB120981SAN and Accelerator Award), the Black Swan Research Initiative of the International Myeloma Foundation, and the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT).
- Published
- 2019