摘要
目的 探究不同年龄的U2小核RNA辅助因子1(U2AF1)突变骨髓增生异常综合征(MDS)患者的临床特征及含砷中药复方(青黄胶囊合补肾益精方)的疗效与预后。方法 回顾性分析2020年11月30日—2023年9月30日于中国中医科学院西苑医院血液科住院并接受含砷中药复方治疗的MDS患者的临床资料。按年龄分层,分别比较年龄<65岁及年龄≥65岁的U2AF1突变型组与野生型组在性别、中医证候、世界卫生组织分型、MDS修订国际预后积分系统(IPSS-R)评分、血常规指标、血清乳酸脱氢酶含量、肾母细胞瘤1(WT1)表达水平、骨髓穿刺及活检指标、染色体预后等级等,并比较含砷中药复方对不同年龄层U2AF1突变型组与野生型组的疗效及年龄对U2AF1突变MDS患者生存预后的影响。结果 共纳入MDS患者201例。年龄<65岁患者104例,包括U2AF1突变型20例、野生型84例;年龄≥65岁患者97例,包括U2AF1突变型19例、野生型78例。年龄<65岁的患者中,与野生型组比较,U2AF1突变型男性及IPSS-R评分≤3分的极低危/低危患者占比更高(P<0.05),平均红细胞体积(MCV)较低(P<0.05),外周血细胞1系减少占比较高(P<0.05)。在年龄≥65岁的患者中,与野生型组比较,U2AF1突变型组MCV较低(P<0.05),骨髓WT1基因表达水平及网状纤维分级为4级的患者占比较高(P<0.05)。含砷中药复方对U2AF1突变患者的总有效率为61.5%(24/39),总反应率为30.8%(12/39);对野生型患者的总有效率为67.9%(110/162),总反应率为29.6%(48/162);总有效率及总反应率差异无统计学意义。Kaplan-Meier生存分析结果表明,年龄<65岁的患者的中位总生存期(mOS)未达到,1、2、3年生存率分别为93.8%、84.4%、84.4%;年龄≥65岁的患者mOS为35月(95%CI:7.559~62.441),1、2、3年生存率分别为66.2%、58.9%、29.4%;年龄≥65岁患者mOS低于年龄<65岁者(P<0.05),而中位无进展生存期差异无统计学意义。结论 U2AF1突变与MDS临床特征密切相关,但是年龄及是否U2AF1突变对含砷中药复方治疗MDS的总有效率及总反应率无明显的影响。年龄为U2AF1突变MDS患者预后的影响因素,即年龄≥65岁患者生存期较短。
Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the fficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM) compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged<65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged<65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P<0.05),a lower mean corpuscular volume(MCV)(P<0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P<0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P<0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P<0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5%(24/39),and the total response rate was 30.8%(12/39).The total effective rate for the wild-type patients was 67.9%(110/162),and the total response rate was 29.6%(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8%,84.4%,and 84.4%,respectively.The m0S of the patients aged≥65 years was 35 months(95% confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2%,58.9%,and 29.4%,respectively.The m0S of patients in the aged≥65 years group was significantly lower than that in the aged<65 years group(P<0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.
作者
张朝畅
刘驰
王德秀
陈卓
吕妍
肖海燕
刘为易
许勇钢
杨秀鹏
麻柔
唐旭东
ZHANG Chaochang;LIU Chi;WANG Dexiu;CHEN Zhuo;LYU Yan;XIAO Haiyan;LIU Weiyi;XU Yonggang;YANG Xiupeng;MA Rou;TANG Xudong(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Graduate School of China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《北京中医药大学学报》
北大核心
2025年第9期1211-1221,共11页
Journal of Beijing University of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(No.82074258,No.82274502)
第二批北京市研究型病房示范建设项目(No.BCRW202108)
中国中医科学院科技创新工程重大攻关项目(No.CI2021A01701)。
关键词
U2小核RNA辅助因子1突变
骨髓增生异常综合征
髓毒劳
青黄散
补肾益精方
生存分析
回顾性研究
U2 small nuclear RNA cofactor 1 mutation
myelodysplastic syndrome
myelotoxic fatigue
Qinghuang Powder
Bushen Yijing Formula
survival analysis
retrospective study
