Abstract

MBL is a common hematological pre-malignant condition that is understudied in screening cohorts. MBL can be classified into low-count (LC-) and high-count (HC-) 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: 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 (HR) and 95% confidence intervals (CIs), adjusting for age and sex. We identified 1,712 (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=0.78) but did among HC-MBL (HR=1.8;95%CI:1.1-3.1,P=0.03). 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<0.001) and 7.7-fold increased risk for lymphoid malignancies (95%CI:3.1-19.2,P<0.001). LC-MBL was associated with 4.3-fold risk of lymphoid malignancies (95%CI:1.4-12.7,P=0.009); HC-MBL had a 74-fold increased risk (95%CI:22-246,P<0.001). In this large screening cohort, we observed similar survival among individuals with and without LC-MBL, yet individuals with LC-MBL have a 4-fold increased risk of lymphoid malignancies. Accumulating evidence indicates that there are clinical consequences to LC-MBL, a condition that affects 8-10 million adults in the United States.

View details for DOI 10.1182/blood.2022016279

View details for PubMedID 35969843