Moreno David F, Pereira Arturo, Tovar Natalia, Cibeira María Teresa, Magnano Laura, Rozman María, López-Guerra Mónica, Colomer Dolors, Martín-Antonio Beatriz, Jiménez-Segura Raquel, Isola Ignacio, Rodríguez-Lobato Luis Gerardo, Oliver-Caldés Aina, Mena Mari Pau, Rosiñol Laura, Bladé Joan, Fernández de Larrea Carlos
Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Cancers (Basel). 2021 Apr 23;13(9):2055. doi: 10.3390/cancers13092055.
We analyzed 171 patients with asymptomatic IgM monoclonal gammopathies (64 with IgM monoclonal gammopathy of undetermined significance-MGUS and 107 with smoldering Waldenström macroglobulinemia - SWM) who had a bone marrow (BM) evaluation performed at diagnosis. Abnormal free-light chain ratio (53% vs. 31%) and mutation prevalence (66% vs. 30%) were higher in patients with SWM. No other differences were found among groups. With a median follow-up of 4.3 years, 14 patients progressed to Waldenström macroglobulinemia, 1 to amyloidosis, and 28 died without progression. The mutation was found in 53% of patients (available in 160 patients). Multivariate analysis showed that immunoparesis (subhazard ratio-SHR 10.2, 95% confidence interval-CI: 4.2-24.8; < 0.001) and BM lymphoplasmacytic infiltration ≥ 20% (SHR: 6, 95% CI: 1.6-22.1; = 0.007) were associated with higher risk of progression. We developed a risk model based on these two risk factors. In the absence of both variables, an ultra-low risk group was identified (SHR 0.1, 95% CI 0.02-0.5; = 0.004), with 3% and 6% of cumulative incidence of progression at 10 and 20 years, respectively. Bootstrap analysis confirmed the reproducibility of these results. This study finds immunoparesis and BM infiltration as biomarkers of progression as well as a low-risk group of progression in asymptomatic IgM monoclonal gammopathies.
我们分析了171例无症状IgM单克隆丙种球蛋白病患者（64例意义未明的IgM单克隆丙种球蛋白病 - MGUS和107例冒烟型华氏巨球蛋白血症 - SWM），这些患者在诊断时均进行了骨髓（BM）评估。SWM患者的异常游离轻链比率（53%对31%）和突变发生率（66%对30%）更高。各组之间未发现其他差异。中位随访4.3年，14例患者进展为华氏巨球蛋白血症，1例进展为淀粉样变性，28例未进展而死亡。53%的患者检测到突变（160例患者可检测）。多因素分析显示，免疫球蛋白缺乏（亚风险比 - SHR 10.2，95%置信区间 - CI：4.2 - 24.8；P < 0.001）和骨髓淋巴细胞浆细胞浸润≥20%（SHR：6，95% CI：1.6 - 22.1；P = 0.007）与更高的进展风险相关。我们基于这两个风险因素开发了一个风险模型。在不存在这两个变量的情况下，确定了一个超低风险组（SHR 0.1，95% CI 0.02 - 0.5；P = 0.004），10年和20年的累积进展发生率分别为3%和6%。自举分析证实了这些结果的可重复性。本研究发现免疫球蛋白缺乏和骨髓浸润是无症状IgM单克隆丙种球蛋白病进展的生物标志物以及低风险进展组。
