骨髓增生异常综合征患者基因突变对地西他滨临床疗效的影响

Effect of gene mutation on the clinical efficacy of decitabine for patients with myelodysplastic syndrome

目的探讨基因突变及相关临床指标对接受地西他滨治疗的骨髓增生异常综合征(MDS)患者预后的影响。方法收集38例初诊MDS患者临床数据及血液、骨髓液等临床标本,基因序列及染色体核型分析结果,应用单因素及多因素统计分析研究MDS患者的反应率及生存时间,回顾性分析临床指标及基因状况对接受地西他滨治疗的MDS患者预后的影响。结果 38例初诊患者,92%存在至少1个突变基因,染色体异常检出率为52.6%。患者接受地西他滨单药治疗或地西他滨联合化疗,中位疗程数为4,患者总反应率为63%(24/38)。多因素分析发现,TET2基因突变患者化疗后反应率较未发生突变患者的反应率高(82%vs 48%),差异有统计学意义(P_单=0.043,P_多=0.034)。随访患者最终死亡12例(32%),所有患者的中位生存时间为27.6个月。多因素生存分析发现,38例MDS患者染色体核型分型好、中等、差的中位生存时间分别为31.4、17.6、10.4个月,IPSS风险分层低危、中危-1、中危-2、高危的中位生存时间分别为31.4、27.6、23.4、11.4个月,血红蛋白≥100 g/L、<100 g/L的中位生存时间分别为31.4、19.4个月,血细胞减少系数0～1、≥2的中位生存时间分别为31.4、17.6个月,差异均有统计学意义(P均<0.05)。TP53基因有无突变患者的中位生存时间分别为16.4、31.4个月,但差异无统计学意义(P=0.097)。结论 TET2基因突变的患者化疗反应率较未突变患者高,TET2基因突变状态对预测反应率具有重要意义。

ObjectiveTo investigate the effect of gene mutation and related clinical indicators on the prognosis of patients w ith myelodysplastic syndromes(M DS).MethodsClinical data of 38 M DS patients w ere collected.Clinical specimens such as blood and genetic sequencing and karyotype analysis of bone marrow fluid w ere also collected.The response rate and survival rate of M DS patients treated w ith decitabine w ere statistically analyzed by single factor and multiple factors using SPSS softw are.The effects of clinical features and gene mutation on the prognosis of M DS patients treated w ith decitabine w ere retrospectively analyzed.Results Among the 38 cases,92%of patients had at least one mutant gene and the detection rate of chromosome abnormality w as 52.6%.Patients accepted monotherapy of decitabine or combined treatment w ith decitabine.The median number of treatment cycles w as 4,and the total response rate w as 63%(24/38).Fourteen patients w ere invalid.M ultifactor analysis found that the response rate of patients w ith TET2 gene mutation w as higher than those w ithout mutation(82%vs 48%,P_s=0.043,P_m=0.034).The follow-up patients ended up w ith 12 deaths(32%).M edian survival time of all patients w as 27.6 months.M ultifactor survival analysis found that chromosome karyotypes w ere good,intermediate and poor in 38 M DS patients and their survival time were 31.4,17.6,10.4 months,respectively.The risk stratification of IPSS were low risk,intermediate-1,intermediate-2,high risk and median survival time w ere 31.4,27.6,23.4,11.4 months,respectively.M edian survival time for patients w ith hemoglobin≥100 g/L and<100 g/L w ere respective 31.4 and 19.4 months.M edian survival time for patients w ith the number of cytopenias w ith 0-1 and greater than 2 w ere respective 31.4 and 17.6 months.The indicators mentioned above w ere statistically different(all P<0.05).M edian survival time of patients w ith and w ithout TP53 mutation w ere16.4 and 31.4 months w ithout statistical difference(P=0.097).ConclusionPatients w ith TET2 gene mutation have higher response rate to chemotherapy than those w ithout mutation.