Abstract

CLL has one of the highest familial-risks among cancers. MBL, the precursor to CLL, has a higher prevalence (13-18%) in families with two or more members with CLL compared to the general population (5-12%). Although, the rate of progression to CLL for high-count MBLs (clonal B-cell count500/L) is ~1-5%/year, no low-count MBLs has been reported to progress to date. We report the incidence and natural history of MBL in relatives from CLL families. In 310 CLL families, we screened 1045 relatives for MBL using highly-sensitive flow cytometry and prospectively followed 449 of them. MBL incidence was directly age- and sex-adjusted to the 2010 United States population. CLL cumulative incidence was estimated using Kaplan-Meier survival curves. At baseline, the prevalence of MBL was 22% (235/1045 relatives). After a median follow-up of 8.1 years among 449 relatives, twelve individuals progressed to CLL with a 5-year cumulative incidence of 1.8%. When considering just the 139 relatives with low-count MBL, the 5-year cumulative incidence increased to 5.7%. Finally, 264 had no MBL at baseline of whom 60 individuals subsequently developed MBL (two high-count and 58 low-count MBLs) with an age- and sex-adjusted incidence of 3.5% after a median of 6 years of follow-up. In a screening cohort of relatives from CLL families, we reported progression from normal to low-count MBL to high-count MBL to CLL, demonstrating that low-count MBL precedes progression to CLL. We estimated a 1.1% annual rate of progression from low-count MBL, which is in excess to that in the general population.

View details for DOI 10.1182/blood.2020006322

View details for PubMedID 33512457