Natural history of monoclonal B-cell lymphocytosis among relatives in CLL families

Susan L. Slager, Mark C. Lanasa, Gerald E. Marti, Sara J. Achenbach, Nicola J. Camp, Fatima Abbasi, Neil E. Kay, Celine M. Vachon, James R. Cerhan, James B. Johnston, Timothy G. Call, Kari G. Rabe, Geffen Kleinstern, Nicholas J. Boddicker, Aaron D. Norman, Sameer A. Parikh, Jose F. Leis, Versha Banerji, Danielle M. Brander, Martha GlennAlessandra Ferrajoli, Karen Curtin, Esteban Braggio, Tait D. Shanafelt, Mary L. McMaster, J. Brice Weinberg, Curtis A. Hanson, Neil E. Caporaso

Research output: Contribution to journalArticlepeer-review


Chronic lymphocytic lymphoma (CLL) has one of the highest familial risks among cancers. Monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, has a higher prevalence (13%-18%) in families with 2 or more members with CLL compared with the general population (5%-12%). Although, the rate of progression to CLL for high-count MBLs (clonal B-cell count ≥500/µL) is ∼1% to 5%/y, no low-count MBLs have 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 US 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, 12 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 (2 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-count 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 of that in the general population.

Original languageEnglish
Pages (from-to)2046-2056
Number of pages11
Issue number15
StatePublished - 15 Apr 2021
Externally publishedYes

Bibliographical note

Funding Information:
This material is based upon work supported by National Institutes of Health grants (National Cancer Institute U01CA118444, P50CA097274, 1K08CA134919; National Institute on Aging R01AG58266); the Intramural Program of the National Cancer Institute; the Veterans Affairs Research Service; and by the CancerCare Manitoba Foundation. The high-risk pedigrees in Utah are made possible because of the Utah Population Database (UPDB), which is supported in part by a National Institutes of Health/National Cancer Institute grant (P30 CA2014), the University of Utah, and from the University of Utah's program in Personalized Health and Center for Clinical and Translational Science. Cancer data come from the Utah Cancer Registry, which is funded by the National Institutes of Health/National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program (HHSN261201800016I), the US Centers for Disease Control and Prevention's National Program of Cancer Registries (cooperative agreement no. NU58DP0063200), with additional support from the University of Utah and Huntsman Cancer Foundation.

Publisher Copyright:
© 2021 American Society of Hematology

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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