游离轻链比值在意义未明的轻链单克隆丙种球蛋白病中的意义：iStopMM筛查研究的流式细胞术亚研究

The significance of free light-chain ratio in light-chain monoclonal gammopathy of undetermined significance: a flow cytometry sub-study of the iStopMM screening study.

作者信息

Óskarsson Jón Þórir, Rögnvaldsson Sæmundur, Thorsteinsdottir Sigrun, Long Thorir Einarsson, Ólafsson Andri, Eythorsson Elias, Jónsson Ásbjörn, Viðarsson Brynjar, Önundarson Páll T, Agnarsson Bjarni A, Pálmason Róbert, Sigurðardóttir Margrét, Þorsteinsdóttir Ingunn, Ólafsson Ísleifur, Harding Stephen J, Durie Brian G M, Love Thorvardur Jon, Kristinsson Sigurdur Y

机构信息

Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

Landspítali University Hospital, Reykjavík, Iceland.

出版信息

Blood Cancer J. 2024 Dec 18;14(1):221. doi: 10.1038/s41408-024-01201-9.

DOI:10.1038/s41408-024-01201-9

PMID:39695077

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11655515/

Abstract

Light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. LC-MGUS is characterized by free light-chain (FLC) levels outside defined reference intervals, indirectly indicating underlying plasma cell (PC) monoclonality. Next-generation flow cytometry (NGF) was used to evaluate clonal PC presence in bone marrow (BM) samples from individuals with LC-MGUS in the iStopMM study, aiming to assess the predictive value of the FLC ratio for clonal PC presence and its prognostic implications. BM samples from 61 individuals with LC monoclonal gammopathy were analyzed. Clonal plasma cells were detected in 53.6% of LC-MGUS samples (n = 28) and in all samples from individuals with more advanced conditions (n = 33). The FLC ratio was predictive of clonal PC presence for kappa-involved FLC ratios (p < 0.05; n = 42), with an optimal cutoff of 3.15 (96.7% sensitivity, 91.7% specificity). Of 195 individuals with kappa-involved LC-MGUS in follow-up within the iStopMM study, none with FLC ratios >1.65 to 3.15 progressed to MM (n = 124), whereas 4/71 (5.6%) with FLC ratios >3.15 progressed over median follow-up of 55 months. These findings support using a kappa-involved FLC ratio cutoff of >3.15 to more accurately identify individuals at increased risk of developing symptomatic PC disorders.

摘要

意义未明的轻链（LC）单克隆丙种球蛋白病（MGUS）是多发性骨髓瘤（MM）及相关疾病的前驱病变。LC-MGUS的特征是游离轻链（FLC）水平超出既定参考区间，间接提示潜在的浆细胞（PC）单克隆性。在iStopMM研究中，采用新一代流式细胞术（NGF）评估LC-MGUS患者骨髓（BM）样本中克隆性PC的存在情况，旨在评估FLC比值对克隆性PC存在情况的预测价值及其预后意义。对61例LC单克隆丙种球蛋白病患者的BM样本进行了分析。在53.6%的LC-MGUS样本（n = 28）以及所有病情更严重患者的样本（n = 33）中检测到了克隆性浆细胞。对于κ型FLC比值，FLC比值可预测克隆性PC的存在（p < 0.05；n = 42），最佳临界值为3.15（敏感性96.7%，特异性91.7%）。在iStopMM研究随访的195例κ型LC-MGUS患者中，FLC比值>1.65至3.15的患者均未进展为MM（n = 124），而FLC比值>3.15的患者中，71例中有4例（5.6%）在中位随访55个月时病情进展。这些发现支持采用>3.15的κ型FLC比值临界值，以更准确地识别有发生有症状PC疾病风险增加的个体。