title: Evaluation of serum markers in the LRF CLL4 trial: β2-microglobulin but not serum free light chains, is an independent marker of overall survival.
abstract: Chronic lymphocytic leukemia (CLL) is characterized by heterogeneous clinical behavior and there is a need for improved biomarkers. The current study evaluated the prognostic significance of serum free light chains (sFLC, kappa, and lambda) and other serum markers (bar, serum thymidine kinase (sTK), soluble CD23, and LDH) together with established biomarkers in 289 patients enrolled into the LRF CLL4 trial. In a multivariable analysis of serum markers alone, higher big and kappa light chains were statistically significant in predicting disease progression and higher blg, and sTK in predicting mortality. In multivariable analysis for overall survival the following were independently significant: β2M levels, immunoglobulin gene (IGHV) mutational status (>98% homology), age, 17p13 deletions (>10%), and CD38 expression. β2M is the only serum marker that retained clear independent value as a biomarker in the LRF CLL4 trial and remains powerfully prognostic requiring evaluation in any future method of risk stratifying patients.
authors.affiliation: a School of Cancer Sciences, University of Birmingham and Heart of England NHS Foundation Trust , Birmingham , UK ;
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.affiliation: b Bournemouth University Clinical Research Unit, Bournemouth University , Bournemouth , UK ;
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.affiliation: c Department of Clinical Biochemistry , Royal Bournemouth Hospital NHS Foundation Trust , Bournemouth , UK ;
authors.forename: Nicola
authors.initials: N
authors.lastname: Marden
authors.affiliation: d Department of Haematology, Belfast City Hospital , Belfast , UK ;
authors.forename: Denis
authors.initials: D
authors.lastname: Alexander
authors.affiliation: e Department of Molecular Biology , Royal Bournemouth Hospital , Bournemouth , UK ;
authors.forename: Zadie
authors.initials: Z
authors.lastname: Davis
authors.affiliation: e Department of Molecular Biology , Royal Bournemouth Hospital , Bournemouth , UK ;
authors.forename: David
authors.initials: D
authors.lastname: Hussey
authors.affiliation: f Department of Cancer Sciences , University of Birmingham , Birmingham , UK ;
authors.forename: Helen
authors.initials: H
authors.lastname: Parry
authors.affiliation: g Binding Site Ltd UK , Birmingham , UK ;
authors.forename: Stephen
authors.initials: S
authors.lastname: Harding
authors.affiliation: h Department of Haemato-Oncology , Institute of Cancer Research , London , UK ;
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.affiliation: i Department of Molecular Biology , Royal Bournemouth Hospital , Bournemouth , UK ;
authors.forename: Joe
authors.initials: J
authors.lastname: Begley
authors.affiliation: j Department of Haematology , Royal Bournemouth Hospital , Bournemouth , UK.
authors.forename: David
authors.initials: D
authors.lastname: Oscier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007147:Immunoglobulin Light Chains; D001613:beta 2-Microglobulin
keywords: Lymphoid leukemia; prognostication; serum free light chains