摘要
目的探讨骨髓增生异常综合征(MDS)白血病转化(LT)的危险因素。方法收集2012年1月至2020年12月中国医学科学院血液病医院MDS诊疗中心确诊、具有完整的临床资料且进行LT情况随访的320例初诊的原发性MDS患者,回顾性分析发生LT的MDS患者初诊时临床和分子学特征以及MDS患者发生LT的危险因素。结果中位随访13.6(0.4~107.3)个月,随访期间共有75例(23.4%)MDS患者发生LT(LT组)。与未发生LT患者(未发生LT组)相比,LT组患者年龄更大(60岁对48岁,P<0.001)、骨髓原始细胞比例更高(7.0%对2.5%,P<0.001)。两组患者中骨髓纤维化(MF-2/3级比例)(13.9%对6.5%,P=0.046)、WHO分型诊断构成比(P<0.001)、修订版国际预后积分系统(IPSS-R)分组(P<0.001)和IPSS-R细胞遗传学分组(P=0.001)比较,差异均有统计学意义。初诊时,LT组和未发生LT组患者中位基因突变数目分别为1(1,3)个、1(0,2)个(P=0.003)。LT组TP53(P=0.034)、DNMT3A(P=0.026)NRAS(P=0.027)、NPM1(P=0.017)基因突变率显著高于未发生LT组。6例患者初诊和LT时两次二代测序结果比较,LT时患者中位基因突变数目增多[2(0~8)个对0.5(0~4)个],中位等位基因突变频率(VAF)较初诊时明显增加。多因素Cox分析显示,骨髓原始细胞比例[以<5%为参照,5%~10%的HR=4.587,95%CI2.214~9.504,P<0.001;>10%的HR=9.352,95%CI4.049~21.600,P<0.001],IPSS-R细胞遗传学分组差和极差(HR=2.603,95%CI1.229~5.511,P=0.012)、DNMT3A突变(HR=4.507,95%CI1.889~10.753,P=0.001)、NPM1突变(HR=3.341,95%CI1.164~9.591,P=0.025)是MDS发生LT的独立危险因素。结论骨髓原始细胞比例高、IPSS-R细胞遗传学分组差和极差、DNMT3A突变、NPM1突变是MDS发生LT的独立危险因素。
Objective To explore the risk factors in leukemia transformation(LT)in those with myelodysplastic syndromes(MDS).MethodsFrom January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center.The clinical features and molecular characteristics are explored.Additionally,a retrospective analysis of risk factors for the development of acute leukemia from MDS was done.ResultsThe median follow-up was13.6(0.4-107.3)months.23.4%(75/320)of the MDS patients had LT group.Significant differences between the LT group and non-LT group can be seen in age(P<0.001),bone marrow blast percentage(P<0.001),bone marrow fibrosis(P=0.046),WHO classification(P<0.001),IPSS-R(P<0.001)and IPSS-R karyotype group(P=0.001).The median number of mutation of LT group was 1(1,3),that in non-LT group was 1(0,2),which had a statistical difference(P=0.003).At the time of the initial diagnosis of MDS,the LT group had higher rates of the TP53 mutation(P=0.034),DNMT3A mutation(P=0.026),NRAS mutation(P=0.027)and NPM1 mutation(P=0.017).Compared with the mutations at first diagnosis and LT of six patients,the number of mutations increased and the variant allele frequencies(VAF)increased significantly in LT patients.Higher bone marrow blast percentage(Refer to<5%,5%-10%:HR=4.587,95%CI 2.214 to 9.504,P<0.001,>10%:HR=9.352,95%CI 4.049 to 21.600,P<0.001),IPSS-R cytogenetic risk groups(HR=2.603,95%CI 1.229-5.511,P=0.012),DNMT3A mutation(HR=4.507,95%CI 1.889-10.753,P=0.001),and NPM1 mutation(HR=3.341,95%CI 1.164-9.591,P=0.025)were all independently associated with LT in MDS patients,according to results of multivariate Cox regression.ConclusionBone marrow blast percentage,IPSS-R cytogenetic risk groups,DNMT3A mutation,and NPM1 mutation are independent risk factors in LT for MDS patients.
作者
赵颂扬
徐泽锋
秦铁军
曲士强
李承文
贾玉娇
潘丽娟
李冰
高清妍
焦蒙
黄慧君
肖志坚
Zhao Songyang;Xu Zefeng;Qin Tiejun;Qu Shiqiang;Li Chengwen;Jia Yujiao;Pan Lijuan;Li Bing;GaoQingyan;Jiao Meng;Huang Huijun;Xiao Zhijian(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2022年第10期818-825,共8页
Chinese Journal of Hematology
基金
国家自然科学基金(82170139、81870104)
中国医学科学院医学与健康科技创新工程项目(2020-I2M-C&T-B-090、2020-I2M-C&T-A-020)。
