title: Normal levels of peripheral CD19(+) CD5(+) CLL-like cells: toward a defined threshold for CLL follow-up -- a GEIL-GOELAMS study.
abstract: BACKGROUND
  The development of flow cytometry as a useful tool for the detection of minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) is potentially hampered by the fact that a normal subset of B-cells with a similar immunophenotype is present in the peripheral blood. This subset of CLL-like cells is not well defined in terms of frequency.
  
  
  METHODS
  Here, we performed a multicenter study with a panel of four-color antibody combinations possibly useful for the detection of MRD in CLL, to establish the levels of normal CLL-like cells in 49 healthy controls. ROC curves established the upper level of such cells at 4 × 10(-4) . The two best combinations were further applied to 419 samples from 117 treated CLL patients.
  
  
  RESULTS
  The combinations CD19/CD5/CD43/CD79b and CD19/CD5/CD81/CD22 appeared very robust and well correlated to enumerate normal CLL-like cells in a lysis no-wash approach. In follow-up samples from CLL patients, they disclosed only 9.8% of the samples within the normal range. In more than 90% of the cases, it was thus possible to report confidently on the absence or presence of MRD in these patients.
  
  
  CONCLUSIONS
  This manuscript reports on the frequency of CD19(+) CD5(+) B-cells in normal peripheral blood and confirms the combinations recommended by the European research initiative on CLL as being performing to assess remaining CLL cells above a threshold of 4 × 10(-4) white blood cells.
authors: Department of Biology, Institut Bergonié, Bordeaux, France.
authors: Françoise
authors: F
authors: Durrieu
authors: Franck
authors: F
authors: Geneviève
authors: Christine
authors: C
authors: Arnoulet
authors: Caren
authors: C
authors: Brumpt
authors: Jean-Claude
authors: JC
authors: Capiod
authors: Michel
authors: M
authors: Degenne
authors: Jean
authors: J
authors: Feuillard
authors: Richard
authors: R
authors: Garand
authors: Amina
authors: A
authors: Kara-Terki
authors: Emilienne
authors: E
authors: Kulhein
authors: Marc
authors: M
authors: Maynadié
authors: Maria-Elena
authors: ME
authors: Ochoa-Noguera
authors: Adriana
authors: A
authors: Plesa
authors: Mikael
authors: M
authors: Roussel
authors: Houchingue
authors: H
authors: Eghbali
authors: Matgorzata
authors: M
authors: Truchan-Graczyk
authors: Marcelo
authors: M
authors: de Carvalho Bittencourt
authors: Pierre
authors: P
authors: Feugier
authors: Marie C
authors: MC
authors: Béné
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry*; D018956:CD5 Antigens / Q000097:blood / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping / Q000592:standards*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D012372:ROC Curve; D012016:Reference Values; D012680:Sensitivity and Specificity; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D018941:Antigens, CD19; D018956:CD5 Antigens; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine