Abnormal serum free light chain ratios are associated with poor survival and may reflect biological subgroups in patients with chronic lymphocytic leukaemia

Authors: Pratt, Guy; Harding, Stephen; Holder, Roger¹; Fegan, Chris²; Pepper, Chris²; Oscier, David³; Gardiner, Anne³; Bradwell, Arthur R.¹; Mead, Graham

Source: British Journal of Haematology, Volume 144, Number 2, January 2009 , pp. 217-222(6)

Publisher: Blackwell Publishing

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Abstract:

Summary

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), β2M (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 κ/λ ratios were adversely prognostic. For patients with mutated IGHV genes, reduced κ/λ 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.

Keywords: chronic lymphocytic leukaemia; serum free light chains; prognosis

Document Type: Research article

DOI: 10.1111/j.1365-2141.2008.07456.x

Affiliations: 1: Department of Primary Care and General Practice, University of Birmingham, Birmingham 2: Department of Haematology, Cardiff University, Cardiff 3: Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK