摘要
目的:探索地西他滨治疗骨髓增生异常综合征(MDS)的临床疗效及预后预测因素。方法:回顾性分析87例接受地西他滨治疗的MDS患者的临床资料。分别采用Q-PCR及测序检测MDS患者h ENT1的mRNA表达及TP53基因的突变情况,分析患者临床特征及分子学指标与地西他滨临床反应的关系。结果:地西他滨中位治疗4(2-17)个疗程,51例(58. 6%)治疗有效,其中CR 17例(19. 5%),PR 12例; mCR 9例,HI 13例,36例(41. 4%)无反应。单因素分析显示,复杂核型、单体核型、7号染色体异常以及1个疗程后Plt数倍增的患者可获得更高的CR率; IPSS相对高危组(中危2+高危)、复杂核型及1个疗程后Plt倍增的患者总体有效率更高。治疗有反应组MDS患者的h ENT1 mRNA表达水平明显高于无反应组[1. 78±1. 45 (2-△△Ct) vs 0. 96±0. 97 (2-△△Ct)](P=0. 002)。在51例有反应组中,CR组的h ENT1 mRNA表达水平高于未获得CR者[2. 58±1. 44(2-△△Ct) vs 1. 39±1. 3(2-△△Ct)](P=0. 005)。在52例相对高危组(中危2+高危)中高h ENT1 mRNA表达的患者中位OS时间显著长于低h ENT1表达的患者(31 vs 12个月)(P <0. 001)。在87例接受地西他滨治疗的患者中,TP53突变者11人(12. 6%)。TP53突变患者总体反应率高(P=0. 04),且更容易获得CR(P <0. 001)。多因素Logistic回归模型显示,复杂核型、1个疗程后Plt数倍增、TP53突变及h ENT1 mRNA高表达是预测地西他滨治疗获得CR的独立预后因素。结论:IPSS分期、复杂核型、1个疗程后Plt数倍增及h ENT1表达、TP53基因突变可预测地西他滨治疗的疗效。
Objective: To explore the clinical efficacy of decitabine for treatment of patients with myelodysplastic syndrome ( MDS) and factors predicting the prognosis.Methods: The clinical data of 87 patients with MDS treated with decitabine were analyzed retrospectively.The hENT1 mRNA expression and TP53 gene mutation were detected by QPCR and gene target sequencing,respectively.The relationship of clinical characteristics and molecular indicators with the clinical response to decitabine was analyzed.Results: In treatment for median 4 ( 2 - 17) courses,a total 51 patients ( 58.6%) showed therapeutic responses,including CR in 17 cases,PR in 12 cases,mCR in 9 cases,HI in 13 cases; 36 ( 41.4%) patients showed non-response.Univariate analysis showed that the patients with the complex karyotype,monosomal karyotype,chomosome 7 abnormality and Plt count doubling after 1 course treatment had a high CR rate,while the patients with relative high risk by IPSS ( intermediate risk 2 + high risk) ,complex karyotype and Plt count doubling after 1 course had much more high overall remission rate ( ORR) .The expression level of hENT1 mRNA in MDS patients with response was significantly higher than that in patients without response [( 1.78 ± 1.45 ( 2 -△△Ct ) vs 0.96 ± 0.97 ( 2 -△△Ct ) ( P = 0.002) ].Among 51 patients with therapeutic response,the expression level of hENT1 mRNA in CR group was higher than that in non-CR group [( 2.58 ± 1.44 ( 2 -△△Ct ) vs 1.39 ± 1.3 ( 2 -△△Ct ) ,P =0.005) ].Among 52 patients in relative high risk ( intermediate risk 2 + high risk) ,the median OS time of patients with high hENT1 mRNA expression was significantly longer than that of patients with low hENT1 mRNA expression ( 31 vs 12 months) ( P<0.001 ) .Among 87 patients received decitabine treatment,the TP53 gene mutation occured in 11 ( 12.6%) patients.The ORR in patients with TP53 mutation was high ( P = 0.04) ,moreover the patients with TP53 mutation more easily gained CR ( P<0.001 ) .Multivariate logistic regression model showed that the complex karyotype, Plt count doubling after 1 course treatment,TP53 mulation and high expression of hENT1 mRNA were the independent prognostic factors for predicting the CR after decitabine treatment.Conclusion: IPSS staging,complex karyotype,Plt count doubling after 1 course treatment and hENT1 mRNA expression,TP53 gene mutation can be used to predict the tharapeutic efficacy of dectitabine for treatment of MDS.
作者
鲍振华
赵洪国
于虹娥
BAO Zhen-Hua;ZHAO Hong-Guo;YU Hong-E(Qiingdao University Medical College,Qiingdao 266000,Shandong Province,China;Department of Hematology,The Affiliated Hospital of Qiingdao University,Qiingdao 266000,Shandong Province,China;Department of Hematology,Haiyang Municipal People's Hospital,Haiyang 265100,Shandong Province,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2018年第6期1702-1707,共6页
Journal of Experimental Hematology