Scientific publications

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Puig N (1), Paiva B (2), Lasa M (3), Burgos L (3), Perez JJ (1), Merino J (3), Moreno C (3), Vidriales MB (1), Toboso DG (1), Cedena MT (4), Ocio EM (1), Lecumberri R (3), García de Coca A (5), Labrador J (6), Gonzalez ME (7), Palomera L (8), Gironella M (9), Cabañas V (10), Casanova M (11), Oriol A (12), Krsnik I (13), Pérez-Montaña A (14), de la Rubia J1 (5), de la Puerta JE (16), de Arriba F (17), Prosper F (3), Martinez-Lopez J (4), Lecrevisse Q (18), Verde J (19), Mateos MV (3), Lahuerta JJ (4), Orfao A (18), San Miguel JF (3).

(1) Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain.
(2) Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBERONC Pamplona, Pamplona, Spain.
(3) Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBERONC Pamplona, Pamplona, Spain.
(4) Hospital 12 de Octubre, Madrid, CNIO, Universidad Complutese CIBERONC, Madrid, Spain.
(5) Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
(6) Hospital Universitario de Burgos, Burgos, Spain.
(7) Hospital de Cabueñes, Gijon, Spain.
(8) Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain.
(9) Hospital Universitari Vall d'Hebron, Barcelona, Spain.
(10) Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
(11) Hospital Costa del Sol, Marbella, Spain.
(12) Institut Català d'Oncologia i Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain.
(13) Hospital Puerta de Hierro, Madrid, Spain.
(14) Hospital Son Espases, Palma, Spain.
(15) Hospital Doctor Peset, Valencia, Spain.
(16) Hospital de Galdakao, Vizcaya, Spain.
(17) Hospital Universitario Morales Meseguer. IMIB-Arrixaca, Murcia, Spain.
(18) Servicio General de Citometría, Universidad de Salamanca, IBSAL, and IBMCC CSIC-USAL, CIBERONC, Salamanca, Spain.
(19) Cytognos SL, Salamanca, Spain.

Magazine: Leukemia

Date: May 1, 2019

Immunology [SP] Hematología y Hemoterapia [SP]

RESUMEN

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 < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis.

Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice.

CITATION  Leukemia. 2019 May;33(5):1256-1267. doi: 10.1038/s41375-018-0308-5. Epub 2018 Dec 12.

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