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Association of Monoclonal B-Cell Lymphocytosis With Future Hematologic Malignancy and Survival
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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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Blood
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Progression and survival of MBL: a screening study of 10 139 individuals
Blood 2022 Oct 13;140(15)1702-1709, SL Slager, SA Parikh, SJ Achenbach, AD Norman, KG Rabe, NJ Boddicker, JE Olson, G Kleinstern, CE Lesnick, TG Call, JR Cerhan, CM Vachon, NE Kay, E Braggio, CA Hanson, TD ShanafeltFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Monoclonal B-cell lymphocytosis (MBL) is typically considered a premalignant hematological condition, with variable to no risk of progression to chronic lymphocytic leukemia based on whether its diagnosis is made during the work-up for lymphocytosis (high count MBL [HC-MBL]) as opposed to a screening survey in individuals with normal counts (low count MBL [LC-MBL]). Using the Mayo Clinic BioBank data, Slager et al screened 10,139 individuals for MBL using an eight-color flow cytometry assay. Of interest, MBL was observed in 17% of individuals, and it was represented by LC-MBL in 95% of patients. This reminds us of the fact that MBL is not rare, but with this being mostly present in individuals with normal counts, the more you look, the more you find. It is unclear whether these data indirectly suggest that the general population should be screened for MBL, as the latter approach may not be sustainable. Using a discovery and a validation cohort, the authors showed that, although only HC-MBL is associated with shorter overall survival, both HC-MBL and LC-MBL are associated with an increased risk of developing lymphoid malignancies, with the risk being greater, of course, for HC-MBL. Based on these data, you may argue that lymphoid malignancies developing in patients with LC-MBL are mostly indolent and not impacting survival; therefore, screening patients with normal counts for MBL would not be cost-effective. On the contrary, the benefit of screening for patients with lymphocytosis seems clearer, thanks to these data. Biological studies are needed to unveil mechanisms of progression in these individuals and to potentially prevent, through vaccination, clinically relevant events. Last but not the least, it is important to remember that the Mayo Clinic database is heavily biased toward Caucasian patients; therefore, these data need to be validated in minority populations underrepresented in clinical research.