Five-Year Follow-up of Monoclonal B-Cell Lymphocytosis (MBL) in Individuals with a Normal Blood Count: Expansion of the Abnormal B-Cell Compartment but No Progressive Disease.

Abstract 59

Monoclonal B-cell Lymphocytosis with a CLL-phenotype (CLL-type MBL) is detected in over 10% of individuals undergoing investigation of a lymphocytosis. The risk of developing progressive CLL requiring treatment is approximately 1% per year. However, monoclonal B-cells can now be readily detected at a level above 1 cell/μL in over 3.5% of adults with normal blood counts, & using highly sensitive techniques in over 20% of elderly individuals. There is currently no reported outcome data for such individuals. The aim of this study was to determine whether individuals with normal blood counts and very low count MBL had any increase in mortality or risk of developing a haematological malignancy. We obtained ethical approval to undertake a linked anonymised investigation of low count MBL cases identified in previous studies. In 2003, 1520 peripheral blood samples from haematologically normal 60–80 year old hospital outpatients were screened & MBL was detected in 105 individuals (78 CLL-type, 27 CD5-negative). Follow-up data is available for 40 CLL-type MBL, 17 CD5-negative MBL & 126 age-matched controls screened for MBL at the same time from the same source with no evidence of abnormal B-cells. After a median follow-up of 65 months (range 0.2–72 months) there have been 51 deaths: 23% (9/40) CLL-type MBL, 35% (6/17) CD5-negative MBL & 29% (36/126) controls. The presence of MBL was not associated with a significantly different overall survival (Log-rank P=0.82). The yearly mortality rate (with 95% CI) was 4.8% (2.5–9.2%) for patients with CLL-type MBL vs. 6.8% (4.7–9.8%, P=0.76) for matched controls. The yearly mortality rate (with 95% CI) was 5.2 % (2.6–10.3%) for patients with a CD5-negative MBL vs. 6.4% (2.6–15.3%) for matched controls. A non-haematological malignancy was detected in 30 cases: 20% (8/40) CLL-type MBL, 6% (1/17) CD5-negative MBL & 17% (21/126) controls. The presence of MBL was also not associated with a significantly risk of developing a non-haematological malignancy (Log-rank P=0.65). Three individuals who had a low level of CLL-type MBL detectable with a normal blood count have been subsequently referred for investigation of a haematological malignancy at 8, 21 and 50 months after initial testing. Two were for referred for investigation of a paraprotein: in both cases the paraprotein isotype was different to the immunoglobulin expressed by the CLL-phenotype cells and neoplastic plasma cells were detected. The third was referred for investigation of a lymphocytosis. In all cases CLL cells were detectable, representing 5-25% of leucocytes. All three individuals are alive with a stable B-lymphocyte count below 5,000/μL and none have required treatment for progressive CLL or myeloma where applicable. One individual who had CD5-negative MBL detected was investigated for a suspected lymphoproliferative disorder 41 months after screening but bone marrow & peripheral blood investigation did not demonstrate any abnormality & the CD5-negative MBL was no longer detectable. One individual from the control group developed MDS. We therefore demonstrate that the presence of a low level of MBL in hospital patients with a normal blood count has no influence on survival or development of non-haematological malignancies compared to age-matched controls. None of the individuals have developed progressive CLL but 7.5% (3/40) cases of low-count CLL-type MBL have shown an expansion of CLL cells over time and been identified clinically through independent referral. The higher rate of detection of MBL or a paraprotein in this group may reflect the closer monitoring applied to regular hospital attenders. These represent the first data concerning outcome for individuals with low levels (<1,500/μL) of CLL-phenotype cells or monoclonal CD5-negative B-cells. The results suggest an increased probability of developing an asymptomatic B-cell abnormality that is routinely detectable but there is no increased risk over a five year period of mortality or development of a B-cell malignancy that requires treatment.