Division of Hematology, Mayo Clinic, Rochester, MN.
Division of Computational Biology, Mayo Clinic, Rochester, MN.
Blood. 2022 Oct 13;140(15):1702-1709. doi: 10.1182/blood.2022016279.
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.
单克隆 B 细胞淋巴增生症(MBL)是一种常见的血液学前恶性疾病,在筛查队列中研究较少。MBL 可以根据 B 细胞克隆的大小分为低计数(LC)和高计数(HC)两种类型。使用 Mayo 诊所生物库,我们筛查了 MBL,并评估了其与未来血液恶性肿瘤和总生存期(OS)的关系。我们采用了包括发现和验证队列的两阶段研究设计。我们使用八色流式细胞术检测法筛查 MBL。从病历中提取血液癌和死亡记录。我们使用 Cox 回归评估相关性,并估计风险比和 95%置信区间(CI),同时调整年龄和性别。我们确定了 1712 名(17%)MBL 患者(95% LC-MBL),OS 的中位随访时间为 34.4 个月,621 人死亡。我们没有观察到 LC-MBL 患者 OS 与 OS 之间存在关联(P =.78),但在 HC-MBL 患者中存在(风险比,1.8;95%CI,1.1-3.1;P =.03)。在发现队列中,中位随访时间为 10.0 年,有 31 人发生血液癌,其中三分之二为淋巴瘤。与对照组相比,MBL 发生血液癌的风险增加了 3.6 倍(95%CI,1.7-7.7;P<.001),发生淋巴瘤的风险增加了 7.7 倍(95%CI:3.1-19.2;P<.001)。LC-MBL 发生淋巴瘤的风险增加了 4.3 倍(95%CI,1.4-12.7;P=.009);HC-MBL 的风险增加了 74 倍(95%CI,22-246;P<.001)。在这项大型筛查队列中,我们观察到 LC-MBL 患者和无 LC-MBL 患者的生存情况相似,但 LC-MBL 患者发生淋巴瘤的风险增加了 4 倍。越来越多的证据表明,LC-MBL 存在临床后果,美国有 800 万至 1000 万人患有这种疾病。