Blood clonal B-cell excess in patients with monoclonal gammopathy of undetermined significance (MGUS): Association with malignant transformation

Fifty-seven patients with monoclonal gammopathy of undetermined significance (MGUS) were analysed for the presence of blood clonal B-cell excess (CBE), defined as a lymphocyte surface membrane kappa/lambda light chain ratio outside the normal range (> 3.5 in kappa-type MGUS and <0.9 in lambda-type MGUS), 15 patients (26%) had a CBE. The patients were followed for a median time of 8.4 years (range 0.5-20.2). Eight of the 15 CBE(+) MGUS patients (53%) developed a B-cell malignancy as compared to 7/42 patients (17%) in the CBE group and the difference in event-free (malignancy-free) observation time was statistically significant (P=0.01). Cox's regression analysis showed that the presence of CBE was the most powerful predictor of progression to a malignant disease. Two patients with a normal kappa/lambda ratio at first test were analysed repeatedly during follow-up. Subsequently, a CBE appeared which gradually increased in size preceding the clinical diagnosis of a malignant disease.