title: Multiparameter flow cytometry for the identification of the Waldenström's clone in IgM-MGUS and Waldenström's Macroglobulinemia: new criteria for differential diagnosis and risk stratification.
abstract: Although multiparameter flow cytometry (MFC) has demonstrated clinical relevance in monoclonal gammopathy of undetermined significance (MGUS)/myeloma, immunophenotypic studies on the full spectrum of Waldenström's Macroglobulinemia (WM) remain scanty. Herein, a comprehensive MFC analysis on bone marrow samples from 244 newly diagnosed patients with an immunoglobulin M (IgM) monoclonal protein was performed, including 67 IgM-MGUS, 77 smoldering and 100 symptomatic WM. Our results show a progressive increase on the number and light-chain-isotype-positive B-cells from IgM-MGUS to smoldering and symptomatic WM (P<.001), with only 1% of IgM-MGUS patients showing >10% B cells or 100% light-chain-isotype-positive B-cells (P<.001). Complete light-chain restriction of the B-cell compartment was an independent prognostic factor for time-to progression in smoldering WM (median 26 months; HR: 19.8, P=0.001) and overall survival in symptomatic WM (median 44 months; HR: 2.6, P=0.004). The progressive accumulation of light-chain-isotype-positive B-cells accompanied the emergence of a characteristic Waldenstrom's phenotype (CD22(+dim) / CD25+ /CD27+ / IgM+) that differed from other B-NHL by negative expression of CD5, CD10, CD11c or CD103. In contrast to myeloma, light-chain-isotype-positive plasma cells in IgM monoclonal gammopathies show otherwise normal antigenic expression. Our results highlight the potential value of MFC immunophenotyping for the characterization of the Waldenström's clone, as well as for the differential diagnosis, risk of progression and survival in WM.
authors.affiliation: 1] Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain [2] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Montes
authors.affiliation: 1] Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain [2] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: R
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: 1] Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain [2] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: E M
authors.initials: EM
authors.lastname: Ocio
authors.affiliation: Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Alonso
authors.affiliation: Complejo Hospitalario de León, León, Spain.
authors.forename: N
authors.initials: N
authors.lastname: de Las Heras
authors.affiliation: Complejo Hospitalario de León, León, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Escalante
authors.affiliation: Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Cuello
authors.affiliation: Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
authors.forename: A G
authors.initials: AG
authors.lastname: de Coca
authors.affiliation: Hospital Comarcal del Bierzo, PonferradaLeón, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Galende
authors.affiliation: Hospital General de Segovia, Segovia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Hernández
authors.affiliation: Hospital Virgen de la Concha, Zamora, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sierra
authors.affiliation: Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.affiliation: Hospital Virgen del Puerto, Plasencia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Pardal
authors.affiliation: Hospital Nuestra Señora de Sonsoles, Ávila, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Bárez
authors.affiliation: Hospital Rio Carrión, Palencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Alonso
authors.affiliation: Hospital Santos Reyes, Aranda de Duero, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Suarez
authors.affiliation: Complejo Asistencial Universitario de Burgos, Burgos, Spain.
authors.forename: T J
authors.initials: TJ
authors.lastname: González-López
authors.affiliation: Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Perez
authors.affiliation: 1] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain [2] Servicio General de Citometría and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Orfao
authors.affiliation: 1] Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain [2] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M-B
authors.initials: MB
authors.lastname: Vidríales
authors.affiliation: 1] Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain [2] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood*; D018570:Risk Assessment; D008258:Waldenstrom Macroglobulinemia / Q000097:blood*
chemical_list: D007075:Immunoglobulin M