title: Defining the prognosis of early stage chronic lymphocytic leukaemia patients.
abstract: Approximately 70% of chronic lymphocytic leukaemia (CLL) patients present with early stage disease, therefore defining which patients will progress and require treatment is a major clinical challenge. Here, we present the largest study of prognostic markers ever carried out in Binet stage A patients (n = 1154) with a median follow-up of 8 years. We assessed the prognostic impact of lymphocyte doubling time (LDT), immunoglobulin gene (IGHV) mutation status, CD38 expression, ZAP-70 expression and fluorescence in situ hybridization (FISH) cytogenetics with regards to time to first treatment (TTFT) and overall survival (OS). Univariate analysis revealed LDT as the most prognostic parameter for TTFT, with IGHV mutation status most prognostic for OS. CD38 expression, ZAP-70 expression and FISH were also prognostic variables; combinations of these markers increased prognostic power in concordant cases. Multivariate analysis revealed that only LDT, IGHV mutation status, CD38 and age at diagnosis were independent prognostic variables for TTFT and OS. Therefore, IGHV mutation status and CD38 expression have independent prognostic value in early stage CLL and should be performed as part of the routine diagnostic workup. ZAP-70 expression and FISH were not independent prognostic markers in early stage disease and can be omitted at diagnosis but FISH analysis should be undertaken at disease progression to direct treatment strategy.
authors.affiliation: School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Pepper
authors.forename: Aneela
authors.initials: A
authors.lastname: Majid
authors.forename: Thet Thet
authors.initials: TT
authors.lastname: Lin
authors.forename: Saman
authors.initials: S
authors.lastname: Hewamana
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.forename: Renata
authors.initials: R
authors.lastname: Walewska
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Simon
authors.initials: S
authors.lastname: Wagner
authors.forename: Ben
authors.initials: B
authors.lastname: Kennedy
authors.forename: Fiona
authors.initials: F
authors.lastname: Miall
authors.forename: Zadie A
authors.initials: ZA
authors.lastname: Davis
authors.forename: Ian
authors.initials: I
authors.lastname: Tracy
authors.forename: Anne C
authors.initials: AC
authors.lastname: Gardiner
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D013997:Time Factors; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
chemical_list: D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1