title: Clonal evolution as detected by interphase fluorescence in situ hybridization is associated with worse overall survival in a population-based analysis of patients with chronic lymphocytic leukemia in British Columbia, Canada.
abstract: This study evaluates prognostic markers as predictors of clonal evolution (CE) and assesses the impact of CE on overall survival (OS) in a population-based cohort of 159 consecutive eligible patients with chronic lymphocytic leukemia (CLL) obtained from the British Columbia Provincial CLL Database. CE was detected by interphase fluorescence in situ hybridization (FISH) in 34/159 patients (21%) with 65% of CE patients acquiring deletion 17p or 11q. CD38 positive status (≥30%) on flow cytometry predicted 2.7 times increased risk of high-risk CE (acquisition of deletion 17p or 11q) on multivariate analysis. Prior CLL therapy was not a significant predictor of CE. CE was associated with 4.1 times greater risk of death when analyzed as a time-dependent variable for OS after adjusting for age, lymphocyte count, and FISH timing. High-risk CE was associated with worse OS while acquisition of low/intermediate-risk abnormalities (trisomy 12, deletion 13q, and IGH translocation) had no difference in OS. Our study demonstrates the negative impact of CE detected by FISH on OS in this population-based cohort. These data provide support for repeating FISH testing during CLL follow-up as patients with high-risk CE have reduced survival and may require closer observation.
authors.affiliation: Division of Hematology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Huang
authors.affiliation: Division of Hematology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Krystal
authors.initials: K
authors.lastname: Bergin
authors.affiliation: Cancer Genetics Laboratory, Pathology and Laboratory Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada; The Pelé Research Institute, Hospital Pequeno Prinicipe, Brazil.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Smith
authors.affiliation: Division of Hematology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; Leukemia/BMT Program of BC, Vancouver General Hospital and British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Alina S
authors.initials: AS
authors.lastname: Gerrie
authors.affiliation: Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Helene
authors.initials: H
authors.lastname: Bruyere
authors.affiliation: Division of Hematology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Chinmay B
authors.initials: CB
authors.lastname: Dalal
authors.affiliation: The Pelé Research Institute, Hospital Pequeno Prinicipe, Brazil.
authors.forename: Daniele K
authors.initials: DK
authors.lastname: Sugioka
authors.affiliation: Cytogenetics Laboratory, Royal Columbian Hospital, New Westminster, BC, Canada.
authors.forename: Monica
authors.initials: M
authors.lastname: Hrynchak
authors.affiliation: Division of Hematology, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Ramadan
authors.affiliation: Cancer Genetics Laboratory, Pathology and Laboratory Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Aly
authors.initials: A
authors.lastname: Karsan
authors.affiliation: Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Gillan
authors.affiliation: Division of Hematology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; Leukemia/BMT Program of BC, Vancouver General Hospital and British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada. Electronic address: ctoze@bccancer.bc.ca.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Toze
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001955:British Columbia / Q000453:epidemiology; D060965:Clonal Evolution; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007399:Interphase; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
keywords: Chronic lymphocytic leukemia; clonal evolution; fluorescence in situ hybridization; overall survival; population; prognosis