Salamatmanesh Mina, McCudden Christopher R, McCurdy Arleigh, Booth Ronald A
Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Division of Biochemistry, The Ottawa Hospital, Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Clin Biochem. 2018 Jan;51:61-65. doi: 10.1016/j.clinbiochem.2017.10.006. Epub 2017 Oct 24.
The International Myeloma Working Group recommendations for monitoring disease progression or response include quantitation of the involved monoclonal immunoglobulin. They have defined the minimum change criteria of ≧25% with an absolute change of no <5g/L for either minimal response or progression. Limited evidence is available to accurately determine the magnitude of change in a monoclonal protein to reflect a true change in clinical status. Here we determined the analytical and biological variability of monoclonal proteins in stable monoclonal gammopathy of undetermined significance (MGUS) patients.
Analytical variability (CVa) of normal protein fractions and monoclonal proteins were assessed agarose gel-based serum protein electrophoresis. Sixteen clinically stable MGUS patients were identified from our clinical hematology database. Individual biological variability (CVi) was determined and used to calculate a monoclonal protein reference change value (RCV).
Analytical variability of the normal protein fractions (albumin, alpha-1, alpha-2, beta, total gamma) ranged from 1.3% for albumin to 5.8% for the alpha-1 globulins. CVa of low (5.6g/L) and high (32.2g/L) concentration monoclonal proteins were 3.1% and 22.2%, respectively. Individual CVi of stable patients ranged from 3.5% to 24.5% with a CVi of 12.9%. The reference change value (RCV) at a 95% probability was determined to be 36.7% (low) 39.6% (high) using our CVa and CVi.
Serial monitoring of monoclonal protein concentration is important for MGUS and multiple myeloma patients. Accurate criteria for interpreting a change in monoclonal protein concentration are required for appropriate decision making. We used QC results and real-world conditions to assess imprecision of serum protein fractions including low and high monoclonal protein fractions and clinically stable MGUS patients to determine CVi and RCV. The calculated RCVs of 36.7% (low) and 39.6% (high) in this study were greater that reported previously and greater than the established criteria for relapse. Response criteria may be reassessed to increase sensitivity and specificity for detection of response.
国际骨髓瘤工作组关于监测疾病进展或缓解的建议包括对受累单克隆免疫球蛋白进行定量分析。他们定义了最低变化标准，即无论是微小缓解还是疾病进展，变化幅度≥25%，绝对变化不低于5g/L。目前关于准确确定单克隆蛋白变化幅度以反映临床状态真实变化的证据有限。在此，我们测定了意义未明的单克隆丙种球蛋白病（MGUS）稳定患者中单克隆蛋白的分析变异性和生物学变异性。
采用基于琼脂糖凝胶的血清蛋白电泳评估正常蛋白组分和单克隆蛋白的分析变异性（CVa）。从我们的临床血液学数据库中识别出16例临床稳定的MGUS患者。测定个体生物学变异性（CVi）并用于计算单克隆蛋白参考变化值（RCV）。
正常蛋白组分（白蛋白、α-1、α-2、β、总γ球蛋白）的分析变异性范围为白蛋白的1.3%至α-1球蛋白的5.8%。低浓度（5.6g/L）和高浓度（32.2g/L）单克隆蛋白的CVa分别为3.1%和22.2%。稳定患者的个体CVi范围为3.5%至24.5%，平均CVi为12.9%。使用我们的CVa和CVi，在95%概率下确定的参考变化值（RCV）为低浓度36.7%，高浓度39.6%。
对MGUS和多发性骨髓瘤患者进行单克隆蛋白浓度的连续监测很重要。为了做出恰当决策，需要有准确的标准来解释单克隆蛋白浓度的变化。我们利用质量控制结果和实际情况评估了包括低、高浓度单克隆蛋白组分在内的血清蛋白组分的不精密度，并对临床稳定的MGUS患者进行测定以确定CVi和RCV。本研究计算出的RCV低浓度为36.7%，高浓度为39.6%，高于先前报道的值，也高于既定的复发标准。可能需要重新评估缓解标准，以提高检测缓解的敏感性和特异性。
