Division of Clinical Pathology, Department of Pathology, Augusta, GA.
Division of Biostatistics and Data Sciences, Medical College of Georgia at Augusta University, Augusta, GA.
Lab Med. 2021 Jul 1;52(4):390-398. doi: 10.1093/labmed/lmaa057.
A proportion of intact immunoglobulin (Ig)-producing multiple myelomas (MMs) was observed to secrete much higher amounts of free light chains (LCs) than usual.
To determine the change point between usual and LC-predominant intact Ig-secreting MMs and other monoclonal gammopathic manifestations and the biological significance of the observation.
We conducted retrospective examination of laboratory findings in 386 MM, 27 smoldering MM, and 179 monoclonal gammopathy of undetermined significance (MGUS) cases that secreted intact Igs. We recorded the highest levels of involved serum free LC, highest ratio of involved to uninvolved LC, highest concentration of involved LC per g of monoclonal Ig, and highest value for ratio of involved to uninvolved LCs divided by the monoclonal Ig concentration. Each data set was sorted into kappa- and lambda LC-associated lesions. Length of time, in months, between diagnosis and last contact with the patients having myeloma was recorded.
Change point analysis of data revealed a subgroup of cases with distinctly higher levels of free LCs. In myelomas, including plasma cell leukemias, 16.4% of myelomas with kappa LCs and 22.3% of myelomas with lambda LCs, the LC secretion was distinctly higher than in the remaining cases, by a combination of 4 parameters, listed herein. Corresponding figures for smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) were 12.5, 27.3, 3.8, and 6.8, respectively. Ten of the 13 (77%) cases of plasma cell leukemia) and all cases of IgD myeloma (n = 4) showed excess secretion of serum free LCs. Among IgG and IgA myelomas, including plasma cell leukemias, the LC-predominant lesions had shorter survival, by an average of 22.5 months.
In total, 18.4% of MMs, including plasma cell leukemias, secrete distinctly higher amounts of serum free LCs than other intact Ig-secreting myelomas and confer significantly lower survival. Quantification of monoclonal serum free LCs may be useful in this subgroup in monitoring progress and potentially in ascertaining minimal residual disease. The findings also stress the need for separate criteria for kappa and lambda LC associated monoclonal gammopathic manifestations. The significantly shorter survival of patients with LC-predominant myelomas warrants consideration in prospective trials of treatments.
观察到一部分完整免疫球蛋白（Ig）产生的多发性骨髓瘤（MM）比通常情况下分泌出更高量的游离轻链（LC）。
确定通常情况下与 LC 优势完整 Ig 分泌性 MM 以及其他单克隆丙种球蛋白病表现之间的变化点，以及观察到的结果的生物学意义。
我们对 386 例 MM、27 例冒烟型 MM 和 179 例单克隆丙种球蛋白病不确定意义（MGUS）病例的实验室检查结果进行了回顾性检查，这些病例均分泌完整 Ig。我们记录了受累血清游离 LC 的最高水平、受累与未受累 LC 的最高比值、受累 LC 每克单克隆 Ig 的最高浓度以及受累与未受累 LC 除以单克隆 Ig 浓度的最高比值。每个数据集均按κ和λ LC 相关病变进行分类。记录从诊断到最后一次与骨髓瘤患者联系的时间（以月为单位）。
数据的变化点分析显示，有一组病例的游离 LC 水平明显升高。在包括浆细胞白血病在内的骨髓瘤中，κ LC 的骨髓瘤占 16.4%，λ LC 的骨髓瘤占 22.3%，与其余病例相比，这两组骨髓瘤的 LC 分泌均明显升高，这是通过本文中列出的 4 个参数组合得出的。冒烟型骨髓瘤（SMM）和单克隆丙种球蛋白病不确定意义（MGUS）的相应数据分别为 12.5%、27.3%、3.8%和 6.8%。在 13 例浆细胞白血病中有 10 例（77%）和所有 IgD 骨髓瘤病例（n=4）均表现出血清游离 LC 的过度分泌。在 IgG 和 IgA 骨髓瘤中，包括浆细胞白血病，LC 优势病变的生存时间更短，平均为 22.5 个月。
总的来说，包括浆细胞白血病在内的 18.4%的 MM 分泌的血清游离 LC 明显高于其他完整 Ig 分泌性骨髓瘤，且生存显著降低。定量检测单克隆血清游离 LC 可能有助于监测此类亚组的病情进展，并可能有助于确定微小残留病。这一发现还强调了为κ和λ LC 相关单克隆丙种球蛋白病表现制定单独标准的必要性。LC 优势型骨髓瘤患者的生存时间显著缩短，这值得在治疗的前瞻性试验中进行考虑。
