Messerich Nora-Medea, Uda Narasimha Rao, Volken Thomas, Cogliatti Sergio, Lehmann Thomas, Holbro Andreas, Benz Rudolf, Graf Lukas, Gupta Vikas, Jochum Wolfram, Demmer Izadora, Rao Tata Nageswara, Silzle Tobias
Department of Intensive Care, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland.
Laboratory of Stem Cells and Cancer Biology, Department of Oncology and Hematology, Medical Research Center, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland.
Cancers (Basel). 2023 Feb 25;15(5):1479. doi: 10.3390/cancers15051479.
In myelofibrosis, the C-reactive protein (CRP)/albumin ratio (CAR) and the Glasgow Prognostic Score (GPS) add prognostic information independently of the Dynamic International Prognostic Scoring System (DIPSS). Their prognostic impact, if molecular aberrations are considered, is currently unknown. We performed a retrospective chart review of 108 MF patients (prefibrotic MF n = 30; primary MF n = 56; secondary MF n = 22; median follow-up 42 months). In MF, both a CAR > 0.347 and a GPS > 0 were associated with a shorter median overall survival (21 [95% CI 0-62] vs. 80 months [95% CI 57-103], < 0.001 and 32 [95% CI 1-63] vs. 89 months [95% CI 65-113], < 0.001). Both parameters retained their prognostic value after inclusion into a bivariate Cox regression model together with the dichotomized Mutation-Enhanced International Prognostic Scoring System (MIPSS)-70: CAR > 0.374 HR 3.53 [95% CI 1.36-9.17], = 0.0095 and GPS > 0 HR 4.63 [95% CI 1.76-12.1], = 0.0019. An analysis of serum samples from an independent cohort revealed a correlation of CRP with levels of interleukin-1β and albumin with TNF-α, and demonstrated that CRP was correlated to the variant allele frequency of the driver mutation, but not albumin. Albumin and CRP as parameters readily available in clinical routine at low costs deserve further evaluation as prognostic markers in MF, ideally by analyzing data from prospective and multi-institutional registries. Since both albumin and CRP levels reflect different aspects of MF-associated inflammation and metabolic changes, our study further highlights that combining both parameters seems potentially useful to improve prognostication in MF.
在骨髓纤维化中，C反应蛋白（CRP）/白蛋白比值（CAR）和格拉斯哥预后评分（GPS）独立于动态国际预后评分系统（DIPSS）增加预后信息。如果考虑分子异常，它们的预后影响目前尚不清楚。我们对108例骨髓纤维化患者进行了回顾性病历审查（纤维化前期骨髓纤维化n = 30；原发性骨髓纤维化n = 56；继发性骨髓纤维化n = 22；中位随访42个月）。在骨髓纤维化中，CAR>0.347和GPS>0均与较短的中位总生存期相关（21个月[95%CI 0 - 62]对80个月[95%CI 57 - 103]，P<0.001；32个月[95%CI 1 - 63]对89个月[95%CI 65 - 113]，P<0.001）。将这两个参数与二分法的突变增强国际预后评分系统（MIPSS）-70一起纳入双变量Cox回归模型后，它们仍保留其预后价值：CAR>0.374，HR 3.53[95%CI 1.36 - 9.17]，P = 0.0095；GPS>0，HR 4.63[95%CI 1.76 - 12.1]，P = 0.0019。对一个独立队列的血清样本分析显示，CRP与白细胞介素-1β水平相关，白蛋白与肿瘤坏死因子-α相关，并表明CRP与驱动突变的变异等位基因频率相关，但与白蛋白无关。白蛋白和CRP作为临床常规中低成本即可获得的参数，值得作为骨髓纤维化的预后标志物进行进一步评估，理想情况下是通过分析前瞻性和多机构注册数据。由于白蛋白和CRP水平反映了骨髓纤维化相关炎症和代谢变化的不同方面，我们的研究进一步强调，结合这两个参数似乎可能有助于改善骨髓纤维化的预后评估。
