Thiele J, Kvasnicka H M, Titius B R, Parpert U, Nebel R, Zankovich R, Dienemann D, Stein H, Diehl V, Fischer R
Institute of Pathology, University of Cologne, Köln, Germany.
Ann Hematol. 1993 Jun;66(6):291-302. doi: 10.1007/BF01695971.
To evaluate the prognostic significance of clinical as well as histological disease features at the time of diagnosis, an immunohistochemical and morphometric study was performed on bone marrow trephine biopsies in 130 patients with Ph(1+)-CML. For identification of all cell elements of the megakaryocytopoiesis we used the monoclonal antibody CD61 (Y2/51) and for the macrophages, the recently characterized antibody PG-M1. Density of argyrophilic fibers was determined per fat cell-free marrow area. Based on a multivariate analysis-derived risk model, the reproducibility of the prognostic score described by Sokal and co-workers was tested, particularly with regard to histological variables. Additionally, we calculated the disease-specific loss in life expectancy. Our prognostic model (Cox model) consisted of the variables: age, spleen size, peripheral erythro-normoblasts, pseudo-Gaucher cells, and fiber density. To assess the validity of this new CML score, a receiver-operating curve (ROC) of sensitivity and specificity was constructed. The improved prognostic efficiency of this newly developed risk model in predicting death within 3 years after diagnosis of CML was demonstrated in comparison with generally accepted staging systems. Immunohistochemistry revealed that not the total number of macrophages, but only the subfraction of pseudo-Gaucher cells exerted a significant impact on survival. Furthermore, it was feasible to calculate the number of atypical micromegakaryocytes and pro- and megakaryoblasts. This abnormal and immature cell population showed a significant correlation with fiber density and prognosis. Finally, the practical value of the Hannover classification was tested. This histological classification enabled a discrimination between two groups with different survival patterns, i.e., granulocyte and/or megakaryocyte-rich subtypes versus subtypes with increase in reticulin and collagen fibers.
为评估诊断时临床及组织学疾病特征的预后意义，对130例Ph(1+)-慢性粒细胞白血病患者的骨髓活检组织进行了免疫组化和形态计量学研究。为识别巨核细胞生成的所有细胞成分，我们使用了单克隆抗体CD61（Y2/51），对于巨噬细胞，则使用了最近鉴定的抗体PG-M1。在无脂肪细胞的骨髓区域测定嗜银纤维密度。基于多变量分析得出的风险模型，测试了Sokal及其同事描述的预后评分的可重复性，特别是关于组织学变量。此外，我们计算了疾病特异性的预期寿命损失。我们的预后模型（Cox模型）由以下变量组成：年龄、脾脏大小、外周红细胞-早幼粒细胞、假戈谢细胞和纤维密度。为评估这个新的慢性粒细胞白血病评分的有效性，构建了敏感性和特异性的受试者工作特征曲线（ROC）。与普遍接受的分期系统相比，该新开发的风险模型在预测慢性粒细胞白血病诊断后3年内死亡方面具有更高的预后效率。免疫组化显示，对生存有显著影响的不是巨噬细胞总数，而是假戈谢细胞亚群。此外，计算非典型微巨核细胞以及原巨核细胞和巨核母细胞的数量是可行的。这个异常和不成熟的细胞群体与纤维密度和预后显示出显著相关性。最后，测试了汉诺威分类法的实用价值。这种组织学分类能够区分具有不同生存模式的两组，即富含粒细胞和/或巨核细胞的亚型与网状纤维和胶原纤维增加的亚型。
