title: Immunoglobulin heavy chain (IGH@) translocations negatively impact treatment-free survival for chronic lymphocytic leukemia patients who have an isolated deletion 13q abnormality.
abstract: Immunoglobulin heavy chain translocations (t(IGH@)) are suggested to portend a poor prognosis in chronic lymphocytic leukemia (CLL). To determine the clinical significance of a t(IGH@) on CLL-specific cytogenetic abnormalities, we analyzed the outcomes of 142 CLL patients referred for fluorescence in situ hybridization (FISH) analysis with our standard FISH panel, which includes testing for a t(IGH@). Whereas patients with unfavorable (deletion 17p, deletion 11q) and intermediate (trisomy 12, normal FISH) cytogenetics with concomitant t(IGH@) had similar median treatment-free survival (TFS) as those without a t(IGH@), patients with deletion 13q (del13q) and a t(IGH@) had significantly worse TFS than those without a t(IGH@): median TFS 4.7 versus 8.0 years, P = 0.03 (hazard ratio 4.21, 95% confidence interval 1.06-16.69 y, P = 0.04 in multivariate analysis after adjusting for age, sex, Rai stage, and white blood cell count). The presence of a t(IGH@) further stratified patients with del13q into two prognostic entities, whereby outcomes of those with coexistent del13q and a t(IGH@) were similar to outcomes of those with high risk cytogenetics. Knowledge of the t(IGH@) status in CLL is therefore of clinical importance, as del13q patients with concomitant t(IGH@) may not retain the previously expected favorable outcome.
authors.affiliation: Division of Hematology, University of British Columbia, Vancouver, Canada.
authors.forename: Alina S
authors.initials: AS
authors.lastname: Gerrie
authors.forename: Helene
authors.initials: H
authors.lastname: Bruyere
authors.forename: Mary Joyce
authors.initials: MJ
authors.lastname: Chan
authors.forename: Chinmay B
authors.initials: CB
authors.lastname: Dalal
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Ramadan
authors.forename: Steven J T
authors.initials: SJ
authors.lastname: Huang
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Toze
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Gillan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003582:Cytogenetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D014178:Translocation, Genetic; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D007143:Immunoglobulin Heavy Chains; D014740:Vidarabine; C024352:fludarabine