Ely Scott, Forsberg Peter, Ouansafi Ihsane, Rossi Adriana, Modin Alvin, Pearse Roger, Pekle Karen, Perry Arthur, Coleman Morton, Jayabalan David, Di Liberto Maurizio, Chen-Kiang Selina, Niesvizky Ruben, Mark Tomer M
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.
Department of Medicine, University of Colorado, Aurora, CO.
Clin Lymphoma Myeloma Leuk. 2017 Dec;17(12):825-833. doi: 10.1016/j.clml.2017.09.010. Epub 2017 Sep 20.
Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice.
Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use. We tested mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC, marrow trephine core biopsy samples were costained for CD138, a plasma cell-specific marker, and Ki-67. Myeloma cells (CD138) were counted as proliferating if coexpressing Ki-67. Retrospective analysis was performed on 151 newly diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma cell proliferation: low (PCPI ≤ 5%, n = 87), and high (PCPI > 5%, n = 64).
Median overall survival (OS) was not reached versus 78.9 months (P = .0434) for the low versus high PCPI groups. Multivariate analysis showed that only high-risk cytogenetics (hazard ratio [HR] = 2.02; P = .023), International Staging System (ISS) stage > I (HR = 2.30; P = .014), and PCPI > 5% (HR = 1.70; P = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely reidentified as high risk by PCPI.
PCPI is a practical method that predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell proliferation for risk stratification.
多发性骨髓瘤（MM）的治疗选择日益增多，但临床结果仍存在异质性。细胞遗传学分析和疾病分期是风险分层的主要方法，但数据表明众多异常之间存在复杂的相互作用。骨髓瘤细胞增殖是一种可预测预后的指标，但现有的方法在临床实践中不可行。
多重免疫组化（mIHC）可同时使用多种免疫染色，已普遍用于临床。我们测试了mIHC作为计算浆细胞增殖指数（PCPI）的方法。通过mIHC，对骨髓环钻活检样本进行CD138（一种浆细胞特异性标志物）和Ki-67的共染色。如果骨髓瘤细胞（CD138）共表达Ki-67，则计为增殖细胞。对151例新诊断的、未接受过治疗的患者进行回顾性分析，根据骨髓瘤细胞增殖情况将其分为两组：低增殖组（PCPI≤5%，n = 87）和高增殖组（PCPI>5%，n = 64）。
低PCPI组与高PCPI组的中位总生存期（OS）分别为未达到和78.9个月（P = 0.0434）。多变量分析显示，只有高危细胞遗传学（风险比[HR]=2.02；P = 0.023）、国际分期系统（ISS）分期>I（HR = 2.30；P = 0.014）和PCPI>5%（HR = 1.70；P = 0.041）对OS有独立影响。64例低危疾病（ISS分期1期，无高危细胞遗传学异常）患者中有23例（36%）通过PCPI被重新确定为高危。
PCPI是一种实用的方法，可预测新诊断骨髓瘤患者的OS，并有助于更广泛地将MM细胞增殖用于风险分层。
