骨髓红系比例≥50%的骨髓增生异常综合征患者临床特征及预后分析

Clinical characteristics and prognosis of patients with myelodysplastic syndrome with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50%

目的分析骨髓红系比例≥50%的骨髓增生异常综合征(MDS-E)患者临床和实验室特征及预后。方法收集2014年5月至2023年6月于中国医学科学院血液病医院确诊的1 436例MDS初治患者病例资料, 回顾性分析MDS-E患者临床特征、分子学等实验室特征以及总生存(OS)情况。结果①MDS-E患者共337例(23.5%), 与骨髓红系比例<50%的MDS(MDS-NE)患者相比, 发病年龄、ANC、PLT更低(P值均<0.05)。MDS-E中诊断伴环状铁粒幼红细胞增多的MDS(MDS-RS)患者比例更高, 多打击TP53基因突变检出率更高(P值均<0.05)。②在MDS-RS患者中, 与MDS-NE相比, MDS-E组复杂染色体核型比例显著减低(0对11.9%, P=0.048), TP53基因突变检出率更低(2.4%对15.1%, P=0.053)。③在TP53突变的MDS患者中, MDS-E患者复杂染色体核型比例(87.5%对63.3%, P=0.002)及多打击TP53突变检出率(84.0%对53.4%, P<0.001)均显著高于MDS-NE患者。④在MDS-RS患者中, MDS-E组的中位OS时间较MDS-NE组更长[未达到对63(95%CI 53~73)个月, P=0.029]。在TP53突变且原始细胞增多的MDS患者中, MDS-E组中位OS时间较MDS-NE组更短[6(95%CI 2~10)个月对12(95%CI 9~15)个月, P=0.022]。⑤多因素分析示, 年龄≥65岁(HR=2.47, 95%CI 1.43~4.26, P=0.001)、MCV≤100 fl(HR=2.62, 95%CI 1.54~4.47, P<0.001)、TP53突变(HR=2.31, 95%CI 1.29~4.12, P=0.005)是MDS-E患者独立于修订的国际预后积分系统(IPSS-R)预后分层的不良预后因素。结论 MDS-RS患者中, MDS-E与更低的复杂染色体核型占比及TP53突变检出率相关, MDS-E组OS时间显著延长。TP53突变的MDS患者中, MDS-E与更高的复杂染色体核型占比和多打击TP53突变检出率相关, 原始细胞增多伴TP53突变的患者中, MDS-E组OS时间显著缩短。年龄≥65岁、MCV≤100 fl及TP53突变是影响MDS-E患者生存的独立不良预后因素。

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome(MDS)with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50%(MDS-E).Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1436 newly diagnosed patients with complete data were included in the study,of which 337(23.5%)patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50%(MDS-NE)(all P<0.05).The proportion of MDS cases with ring sideroblasts(MDS-RS)was higher in the MDS-E group than in the MDS-NE group,and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group(all P<0.05).Among patients with MDS-RS,the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group(0 vs 11.9%,P=0.048 and 2.4%vs 15.1%,P=0.053,respectively).Among patients with TP53 mutations,the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group(87.5%vs 64.6%,P=0.003 and 84.0%vs 54.2%,P<0.001,respectively).Survival analysis of patients with MDS-RS found that the overall survival(OS)in the MDS-E group was better than that in the MDS-NE group[not reached vs 63(95%CI 53.3-72.7)months,P=0.029].Among patients with TP53 mutations and excess blasts,the OS in the MDS-E group was worse than that in the MDS-NE group[6(95%CI 2.2-9.8)months vs 12(95%CI 8.9-15.1)months,P=0.022].Multivariate analysis showed that age of≥65 years(HR=2.47,95%CI 1.43-4.26,P=0.001),mean corpuscular volume(MCV)of≤100 fl(HR=2.62,95%CI 1.54-4.47,P<0.001),and TP53 mutation(HR=2.31,95%CI 1.29-4.12,P=0.005)were poor prognostic factors independent of the Revised International Prognostic Scoring System(IPSS-R)prognosis stratification in patients with MDS-E.Conclusion:Among patients with MDS-RS,MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations,and the OS in the MDS-E group was longer than that in the MDS-NE group.Among patients with TP53 mutations,MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations,and among TP53-mutated patients with excess blasts,the OS in the MDS-E group was shorter than that in the MDS-NE group.Age of≥65 years,MCV of≤100 fl,and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.