title: A GEIL flow cytometry consensus proposal for quantification of plasma cells: application to differential diagnosis between MGUS and myeloma.
abstract: BACKGROUND
  Flow cytometry is the sole available technique for quantification of tumor plasma-cells in plasma-cell disorders, but so far, no consensus technique has been proposed. Here, we report on a standardized, simple, robust five color flow cytometry protocol developed to characterize and quantify bone marrow tumor plasma-cells, validated in a multicenter manner.
  
  
  METHODS
  CD36 was used to exclude red blood cell debris and erythroblasts, CD38 and CD138 to detect plasma-cells, immunoglobulin light chains, CD45, CD56, CD19, and CD117 + CD34 to simultaneously characterize abnormal plasma-cells and quantify bone marrow precursors. This approach was applied in nine centers to 229 cases, including 25 controls.
  
  
  RESULTS
  Tumor plasma-cells were detected in 96.8% of cases, all exhibiting an immunoglobulin peak over 1g/L. Calculation of a plasma-cells/precursors (PC/P) ratio allowed quantification of the plasma-cell burden independently from bone marrow hemodilution. The PC/P ratio yielded the best results in terms of sensitivity (81%) and specificity (84%) for differential diagnosis between MGUS and myeloma, when compared with other criteria. Combination of both the PC/P ratio and percentage of abnormal plasma-cells allowed the best differential diagnosis, but these criteria were discordant in 25% cases. Indirect calculation of CD19 negative PC/R ratio gave the best results in terms of sensitivity (87%).
  
  
  CONCLUSIONS
  This standardized multiparameter flow cytometric approach allows for the detection and quantification of bone marrow tumor plasma-cell infiltration in nearly all cases of MGUS and myeloma, independently of debris and hemodilution. This approach may also prove useful for the detection of minimal residual disease.
authors.affiliation: Laboratoire d'Hématologie, CHU Limoges, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Frébet
authors.forename: Julie
authors.initials: J
authors.lastname: Abraham
authors.forename: Franck
authors.initials: F
authors.lastname: Geneviève
authors.forename: Pascale
authors.initials: P
authors.lastname: Lepelley
authors.forename: Sylvie
authors.initials: S
authors.lastname: Daliphard
authors.forename: Valérie
authors.initials: V
authors.lastname: Bardet
authors.forename: Sophie
authors.initials: S
authors.lastname: Amsellem
authors.forename: Julien
authors.initials: J
authors.lastname: Guy
authors.forename: Francois
authors.initials: F
authors.lastname: Mullier
authors.forename: Francoise
authors.initials: F
authors.lastname: Durrieu
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Venon
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Faucher
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
authors.forename: Jean
authors.initials: J
authors.lastname: Feuillard
mesh_terms: D019046:Bone Marrow Neoplasms / Q000276:immunology / Q000473:pathology*; D003937:Diagnosis, Differential; D005434:Flow Cytometry / Q000379:methods* / Q000592:standards*; D006801:Humans; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity