title: Peripheral blood 8 colour flow cytometry monitoring of hairy cell leukaemia allows detection of high-risk patients.
abstract: Although purine analogues have significantly improved the outcome of hairy cell leukaemia (HCL) patients, 30-40% relapse, illustrating the need for minimal residual disease (MRD) markers that can aid personalized therapeutic management. Diagnostic samples from 34 HCL patients were used to design an 8-colour flow cytometry (8-FC) tube for blood MRD (B/RD) analysis (188 samples) which was compared to quantitative IGH polymerase chain reaction (Q-PCR) on 83 samples and to qualitative consensus IGH PCR clonality analysis on 165 samples. Despite heterogeneous HCL phenotypes at diagnosis, discrimination from normal B lymphocytes was possible in all cases using a single 8-FC tube, with a robust sensitivity of detection of 10(-4) , comparable to Q-PCR at this level, but preferable in terms of informativeness, simplicity and cost. B/RD assessment of 15 patients achieving haematological complete remission after purine analogues was predictive of a clinically significant relapse risk: with a median follow-up of 95 months; only one of the nine patients with reproducible 8-FC B/RD levels below 10(-4) (B/RD(neg) ) relapsed, compared to 5/6 in the B/RD(pos) group (P = 0.003). These data demonstrate the clinical interest of a robust 8-FC HCL B/RD strategy that could become a surrogate biomarker for therapeutic stratification and new drug assessment, which should be evaluated prospectively.
authors.affiliation: Laboratoire d'Hématologie and CNRS UMR8147, Hôpital Necker - Enfants Malades, Université Paris Descartes, 149 rue de Sèvres, 75743, Paris Cedex 15, France; INSERM UMR1098, Université de Franche-Comté, EFS-B/FC Plateforme de BioMonitoring, 1 Bd Fleming, 25000, Besançon, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Garnache Ottou
authors.forename: Marie-Olivia
authors.initials: MO
authors.lastname: Chandesris
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lhermitte
authors.forename: Céline
authors.initials: C
authors.lastname: Callens
authors.forename: Kheira
authors.initials: K
authors.lastname: Beldjord
authors.forename: Marlene
authors.initials: M
authors.lastname: Garrido
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Bedin
authors.forename: Chantal
authors.initials: C
authors.lastname: Brouzes
authors.forename: Sarah
authors.initials: S
authors.lastname: Villemant
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Rubio
authors.forename: Coralie
authors.initials: C
authors.lastname: Belanger
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Deau
authors.forename: François
authors.initials: F
authors.lastname: Lefrère
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.forename: Bruno
authors.initials: B
authors.lastname: Varet
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012008:Recurrence; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor
keywords: blood minimal residual disease; hairy cell leukaemia; multicolour flow cytometry