title: Abnormal serum free light chain ratios are associated with poor survival and may reflect biological subgroups in patients with chronic lymphocytic leukaemia.
abstract: The measurement of immunoglobulin serum free light chains (sFLC) has prognostic significance in plasma cell dyscrasias but its role in chronic lymphocytic leukaemia (CLL) is unknown. This retrospective study from three UK hospitals analysed sFLC in 181 untreated/pre-treatment CLL patients and 78 treated CLL patients, with samples taken later in their disease. An abnormal sFLC ratio was significantly associated with poor overall survival for the 181 untreated/pre-treatment patients (P = 0.0001) and for all patients (P = 0.002), irrespective of cause of death. Using multivariate analysis (n = 194), four independent prognostic variables for overall survival were identified namely Zap-70 (P = 0.0001), beta2M (P = 0.01), IGHV mutation status (P = 0.017) and an abnormal sFLC ratio (P = 0.024). For CLL patients with unmutated IGHV genes, elevated kappa/lambda ratios were adversely prognostic. For patients with mutated IGHV genes, reduced kappa/lambda ratios were adversely prognostic and associated with the poor prognostic IGHV3-21, IGHV3-48 and IGHV3-53 subgroups, suggesting an abnormal sFLC ratio may reflect biological subgroups within CLL. Abnormal sFLC ratios need to be studied prospectively in CLL patients and the biological rationale for their abnormality investigated.
authors.affiliation: CRUK Institute for Cancer Studies, University of Birmingham, Birmingham, UK. guy.pratt@heartofengland.nhs.uk
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.forename: Stephen
authors.initials: S
authors.lastname: Harding
authors.forename: Roger
authors.initials: R
authors.lastname: Holder
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
authors.forename: Chris
authors.initials: C
authors.lastname: Pepper
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.forename: Anne
authors.initials: A
authors.lastname: Gardiner
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Bradwell
authors.forename: Graham
authors.initials: G
authors.lastname: Mead
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000097:blood; D001613:beta 2-Microglobulin
chemical_list: D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D001613:beta 2-Microglobulin; D051746:ZAP-70 Protein-Tyrosine Kinase