ROCHESTER, MN – About 10% of chronic lymphocytic leukemia (CLL) patients report a first-degree relative with the cancer or a related lymphoproliferative disorder, according to a new study, which emphasized that CLL and its precursor, monoclonal B-cell lymphocytosis (MBL), have underlying heritable predispositions.

The report in Blood Cancer Journal pointed out that serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but the role of those measures in susceptibility to CLL is not clear.1

Mayo Clinic-led researchers investigated differences between sFLC measurements in pre-treatment serum from five groups to investigate the association of sFLC with familial and sporadic CLL. Those included:

  • familial CLL with 154 participants;
  • sporadic CLL, with 302 participants;
  • familial MBL, with 87 participants;
  • unaffected first-degree relatives from CLL/MBL families, with 263 participants, and
  • the 15,396-member reference population.

Families were recruited through the Genetic Epidemiology of CLL consortium2at six institutions, including VAMCs. Institutions providing participants were the Mayo Clinic, M.D. Anderson Cancer Center, the National Cancer Institute (NCI), University of Minnesota/Minneapolis VA Medical Center, Duke University/Durham, NC, VA Medical Center and University of Utah. 

Researchers compared the percentage of participants having elevated monoclonal and polyclonal sFLCs using age-stratified and age- and sex-adjusted logistic regression models. The study team determined that, in age groups older than 50-years-old,  monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p’s < 0.05).

“However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p’s > 0.05),” the authors noted.

The study also reported that unaffected relatives and MBL cases from CLL/MBL families, ages older than 60-years-old, presented with elevated monoclonal sFLC, compared to the reference population (p’s < 0.05).

“This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls,” researchers wrote. “Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.”

Background information in the report noted that, in the general population, MBL increases with age with a prevalence of 5–9% in individuals older than 60 years and that past research has reported MBL to be higher among first-degree relatives from CLL families, occurring at a higher rate in high-risk CLL families, which implies a shared inherited risk.

The authors added that paraproteins, usually aligned with plasma cell disorders, have also been found to be prevalent in other B-cell malignancies, such as CLL.

“A prospective study showed an abnormal rFLC can be detected several years before the actual diagnosis of CLL in a significant percentage of patients,” the researchers explained. “Thus, sFLC measurements have been implicated in detection and prognosis of CLL, however, few studies evaluating sFLCs and risk of CLL (or MBL) have been performed.”

  1. Clay-Gilmour, A.I., Rishi, A.R., Goldin, L.R. et al.Association of elevated serumfree light chains with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Blood Cancer J. 959 (2019) doi:10.1038/s41408-019-0220-x