title: Minimal residual disease detection with tumor-specific CD160 correlates with event-free survival in chronic lymphocytic leukemia.
abstract: In chronic lymphocytic leukemia (CLL), the detection of minimal residual disease (MRD) correlates with outcome in the trial setting. However, MRD assessment does not guide routine clinical management and its assessment remains complex. We incorporated detection of the B cell, tumor-specific antigen CD160 to develop a single-tube, flow cytometry assay (CD160FCA) for CLL MRD to a threshold of 10(-4) to 10(-5). One hundred and eighty-seven patients treated for CLL were enrolled. Utilizing the CD160FCA methodology, there was a high level of comparison between blood and bone marrow (R=0.87, P<0.001). In a validation cohort, CD160FCA and the international standardised approach of the European Research Initiative on CLL group demonstrated high concordance (R=0.91, P<0.01). Patients in complete remission (CR) and CD160FCA negative had longer event-free survival (EFS) (63 vs 16 months, P<0.01) and prolonged time to next treatment (60 vs 15 months, P<0.001) vs MRD positive patients; with a median time to MRD positivity of 36 months. In multivariate analysis, CD160FCA MRD detection was independently predictive of EFS in patients in CR and even predicted EFS in the good-risk cytogenetic subgroup. CD160FCA offers a simple assay for MRD detection in CLL and gives prognostic information across different CLL risk groups.
authors.affiliation: 1] Department of Haemato-Oncology and Immunophenotyping Section, Barts Health NHS Trust, London, UK [2] Pathology Group, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: T W
authors.initials: TW
authors.lastname: Farren
authors.affiliation: Laboratoire de Thérapie Cellulaire, Institut Jean Godinot, 1 Avenue du Général Koenig, Reims, France.
authors.forename: J
authors.initials: J
authors.lastname: Giustiniani
authors.affiliation: Pathology Group, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Fanous
authors.affiliation: Pathology Group, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Haemato-Oncology and Immunophenotyping Section, Barts Health NHS Trust, London, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Macey
authors.affiliation: Department of Haematology, The Royal Free Hospital, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Wright
authors.affiliation: Department of Haematology, The Royal Free Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Prentice
authors.affiliation: UCL Cancer Institute, University College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Nathwani
authors.affiliation: 1] Department of Haemato-Oncology and Immunophenotyping Section, Barts Health NHS Trust, London, UK [2] Pathology Group, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: S G
authors.initials: SG
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D002699:Chlorambucil / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D011971:Receptors, Immunologic / Q000235:genetics
chemical_list: D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D011971:Receptors, Immunologic; D002699:Chlorambucil