Monoclonal B-cell lymphocytosis is closely related to chronic lymphocytic leukaemia and may be better classified as early-stage CLL

Abstract

The World Health Organization classification uses a cut-off point of 5·0 × 10(9)/l cells with a chronic lymphocytic leukaemia (CLL)-phenotype in peripheral blood to discriminate between monoclonal B-lymphocytosis (MBL) and B-CLL. This study analysed 298 MBL patients by multi-parameter flow cytometry, chromosome banding analysis (CBA)/fluorescence in situ hybridization (FISH), and IGHV mutation status and compared them with 356 CLL patients. In MBL, CBA more frequently revealed a normal karyotype and FISH identified less frequently del(6q), del(13q) (as sole alterations), and del(17)(p13). Within the MBL cohort, a shorter time to treatment (TTT) was found for ZAP-70-positivity, 14q32/IGH-translocations (CBA), del(11)(q22·3) (FISH) and unmutated IGHV status. Higher CD38 and ZAP-70 expression, del(11)(q22·3) (FISH), trisomy 12 (FISH), and 14q32/IGH-translocations (CBA) were correlated with a shorter TTT in the combined cohort (MBL + CLL); a sole del(13)(q14) (FISH) correlated with longer TTT. Regarding overall survival, unmutated IGHV status and 'other' alterations (CBA) had an adverse impact. There was no correlation between the concentration of CLL-cells and TTT or overall survival. Multivariate analysis confirmed a negative impact on TTT for del(11)(q22·3)/ATM, trisomy 12 (both by FISH), and 14q32/IGH-translocations by CBA. These data emphasize a close relationship between MBL and CLL regarding clinically relevant parameters and provide no evidence to strictly separate these entities by a distinct threshold of clonal B-cells.