Evaluation of serum markers in the LRF CLL4 trial: β2-microglobulin but not serum free light chains, is an independent marker of overall survival

Research output: Contribution to journalArticle


  • Peter Thomas
  • Nicola Marden
  • Denis Alexander
  • Zadie Davis
  • David Hussey
  • Stephen Harding
  • Daniel Catovsky
  • Joe Begley
  • David Oscier

Colleges, School and Institutes

External organisations

  • Bournemouth University Clinical Research Unit
  • Department of Haematology, Belfast City Hospital , Belfast , UK
  • Department of Clinical Biochemistry, Royal Bournemouth Hospital NHS Foundation Trust, Bournemouth, UK
  • Department of Molecular Biology, Royal Bournemouth Hospital, Bournemouth, UK
  • Department of Molecular Biology, Royal Bournemouth Hospital, Bournemouth, UK
  • The Binding Site Group Ltd, Birmingham, United Kingdom; Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, United Kingdom.
  • Department of Haemato-Oncology, Institute of Cancer Research, London, UK
  • Department of Molecular Biology, Royal Bournemouth Hospital, Bournemouth, UK
  • Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK


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.


Original languageEnglish
Pages (from-to)2342-2350
Number of pages9
JournalLeukemia and Lymphoma
Issue number10
Publication statusPublished - 8 Feb 2016


  • Adult, Aged, Aged, 80 and over, Antineoplastic Agents/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor, Female, Humans, Immunoglobulin Light Chains/blood, Leukemia, Lymphocytic, Chronic, B-Cell/blood, Male, Middle Aged, Prognosis, Randomized Controlled Trials as Topic, Survival Analysis, Treatment Outcome, beta 2-Microglobulin/blood