TY - JOUR
T1 - Abnormal serum free light chain ratios are associated with poor survival and may reflect biological subgroups in patients with chronic lymphocytic leukaemia
AU - Pratt, Guy
AU - Harding, S
AU - Holder, Roger
AU - Fegan, C
AU - Pepper, C
AU - Oscier, D
AU - Gardiner, A
AU - Bradwell, Arthur
AU - Mead, Graham
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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), beta 2M (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.
AB - 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), beta 2M (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.
KW - chronic lymphocytic leukaemia
KW - serum free light chains
KW - prognosis
U2 - 10.1111/j.1365-2141.2008.07456.x
DO - 10.1111/j.1365-2141.2008.07456.x
M3 - Article
C2 - 19016722
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
SN - 1365-2141
VL - 144
SP - 217
EP - 222
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 2
ER -