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. 2022 Oct 13;140(15):1702-1709.
doi: 10.1182/blood.2022016279.

Progression and survival of MBL: a screening study of 10 139 individuals

Susan L Slager  1   2 , Sameer A Parikh  1 , Sara J Achenbach  3 , Aaron D Norman  4 , Kari G Rabe  3 , Nicholas J Boddicker  2 , Janet E Olson  4 , Geffen Kleinstern  2   5 , Connie E Lesnick  1 , Timothy G Call  1 , James R Cerhan  4 , Celine M Vachon  4 , Neil E Kay  1 , Esteban Braggio  6 , Curtis A Hanson  7 , Tait D Shanafelt  8
Affiliations

Progression and survival of MBL: a screening study of 10 139 individuals

Susan L Slager et al. Blood. .

Abstract

Monoclonal B-cell lymphocytosis (MBL) is a common hematological premalignant condition that is understudied in screening cohorts. MBL can be classified into low-count (LC) and high-count (HC) types based on the size of the B-cell clone. Using the Mayo Clinic Biobank, we screened for MBL and evaluated its association with future hematologic malignancy and overall survival (OS). We had a two-stage study design including discovery and validation cohorts. We screened for MBL using an eight-color flow-cytometry assay. Medical records were abstracted for hematological cancers and death. We used Cox regression to evaluate associations and estimate hazard ratios and 95% confidence intervals (CIs), adjusting for age and sex. We identified 1712 (17%) individuals with MBL (95% LC-MBL), and the median follow-up time for OS was 34.4 months with 621 individuals who died. We did not observe an association with OS among individuals with LC-MBL (P = .78) but did among HC-MBL (hazard ratio, 1.8; 95% CI, 1.1-3.1; P = .03). Among the discovery cohort with a median of 10.0 years follow-up, 31 individuals developed hematological cancers with two-thirds being lymphoid malignancies. MBL was associated with 3.6-fold risk of hematological cancer compared to controls (95% CI, 1.7-7.7; P < .001) and 7.7-fold increased risk for lymphoid malignancies (95% CI:3.1-19.2; P < .001). LC-MBL was associated with 4.3-fold risk of lymphoid malignancies (95% CI, 1.4-12.7; P = .009); HC-MBL had a 74-fold increased risk (95% CI, 22-246; P < .001). In this large screening cohort, we observed similar survival among individuals with and without LC-MBL, yet individuals with LC-MBL have a fourfold increased risk of lymphoid malignancies. Accumulating evidence indicates that there are clinical consequences to LC-MBL, a condition that affects 8 to 10 million adults in the United States.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Image 1
Graphical abstract
Figure 1
Figure 1.
Prevalence of MBL by age groups (A), by sex (B), and by self-reported race (C).
Figure 2
Figure 2.
Boxplots showing the distribution of percent clonal B-cells for each immunophenotype. Distribution: n = 1451 CLL-like MBL clones, n = 92 atypical MBL clones, and n = 257 non–CLL-like MBL clones. Eighty-five individuals had >1 immunophenotype and thus were included in more than one group.
Figure 3
Figure 3.
Cumulative incidence of cancers adjusted for competing risk of death. Cumulative incidence of hematological cancers (A), cumulative incidence of lymphoid cancers (B).
Figure 4
Figure 4.
Overall survival. OS adjusted for age and sex between MBL and controls (A), between HC-MBL,and controls (B), between LC-MBL and controls (C), between atypical MBL and controls (D), between CLL-like MBL and controls (E), and between non–CLL-like MBL and controls (F).
Figure 5
Figure 5.
Change in clonal counts among 48 individuals with CLL-like MBL at both baseline and follow-up evaluation. (A) Individuals (n = 27) whose percent clonal B-cell count was <10% both time points. (B) Individuals (n = 21) who had at least one time point whose percent clonal B-cell count was >10%.
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Comment in

References

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