Department of Epidemiology, Biostatistics and Community Health Sciences, Faculty of Health Sciences, School of Public Health, Ben Gurion University of the Negev, Beer Sheva, Israel.
Tel -Aviv Sourasky (Ichilov) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Clin Exp Med. 2024 Aug 24;24(1):198. doi: 10.1007/s10238-024-01471-4.
The clinical significance of an abnormal free light chain (FLC) test, performed due to unspecific complains in the absence of a known plasma cell dyscrasia (PCD) or lymphoproliferative disease (LPD), is not fully elucidated. We investigated the importance of an abnormal FLC ratio (FLC-R) in this setting. Patients registered in the Maccabi Healthcare Services database, tested for FLC during 2007-2023 without previously documented PCD/LPD or increased total protein (TP) level, were reviewed. Demographics, co-morbidities, and laboratory tests were recorded. FLC-R was defined as normal (0.26-1.65) or slightly (slAb 0.1-0.26/1.65-4), moderately (mAbn 0.1-0.05/4-8) and significantly abnormal (sigAb- < 0.05 or > 8). Factors associated with PCD/LPD and overall survival were identified. In total, 8,661 patients, 2,215 (25.6%) with abnormal FLC-R [2,090 (24.1%)-slAb, 65 (0.75%)-mAbn and 60 (0.7%)-sigAb], were analyzed. Almost none had anemia nor acute renal failure. 14% had concomitant increased immunoglobulins. Within a median follow-up of 52 months, 943 were diagnosed with PCD (816-MGUS, 127-MM/Amyloidosis/plasmacytoma) and 48 with LPD. Median time to PCD and LPD were 19 and 28 months. Multivariate analysis found slAb (HR = 1.8, CI95%:1.53-2.12, p < 0.001), mAbn (HR = 6.3, CI95%:4.16-9.53, p < 0.001), and sigAb FLC (HR = 10.4, CI95%:7.0-15.35, p < 0.001), to be associated with PCD/LPD diagnosis. Decreased IgG, increased IgA, and concomitant comorbidities predicted PCD, whereas increased IgM predicted LPD. Older age, male gender, anemia, decreased albumin, increased IgG and concomitant comorbidities, predicted shorter survival. Our large study emphasizes the independent clinical significance of abnormal FLC-R as a predictor of PCD/LPD diagnosis even in patients with normal TP level, promoting early detection of PCD/LPD.
在没有已知浆细胞疾病（PCD）或淋巴增生性疾病（LPD）的情况下，由于非特异性投诉而进行异常游离轻链（FLC）检测的临床意义尚未完全阐明。我们研究了在此情况下异常 FLC 比值（FLC-R）的重要性。对 2007 年至 2023 年期间在 Maccabi 医疗保健服务数据库中接受 FLC 检测且无先前记录的 PCD/LPD 或总蛋白（TP）水平升高的患者进行了回顾性分析。记录了人口统计学、合并症和实验室检查结果。FLC-R 定义为正常（0.26-1.65）或轻度（slAb0.1-0.26/1.65-4）、中度（mAbn0.1-0.05/4-8）和显著异常（sigAb- < 0.05 或 > 8）。确定了与 PCD/LPD 和总生存期相关的因素。共分析了 8661 例患者，其中 2215 例（25.6%）FLC-R 异常[2090 例（24.1%）-slAb、65 例（0.75%）-mAbn 和 60 例（0.7%）-sigAb]。几乎没有患者出现贫血或急性肾衰竭。14%的患者同时伴有免疫球蛋白升高。中位随访 52 个月期间，943 例被诊断为 PCD（816-MGUS、127-MM/淀粉样变性/浆细胞瘤），48 例被诊断为 LPD。PCD 和 LPD 的中位时间分别为 19 个月和 28 个月。多变量分析发现，slAb（HR=1.8，95%CI：1.53-2.12，p<0.001）、mAbn（HR=6.3，95%CI：4.16-9.53，p<0.001）和 sigAb FLC（HR=10.4，95%CI：7.0-15.35，p<0.001）与 PCD/LPD 诊断相关。IgG 减少、IgA 增加和同时存在合并症预测 PCD，而 IgM 增加预测 LPD。年龄较大、男性、贫血、白蛋白减少、IgG 增加和同时存在合并症与生存时间缩短相关。我们的大型研究强调了异常 FLC-R 作为 PCD/LPD 诊断预测因子的独立临床意义，即使在 TP 水平正常的患者中也是如此，这有助于早期发现 PCD/LPD。
