地西他滨治疗伴DNA甲基转移酶基因突变的骨髓增生异常综合征患者的疗效分析

Outcomes of DNMT3A^+ Myelodysplastic Syndrome Patients Treated with Decitabine

目的:探讨单用地西他滨治疗伴DNA甲基转移酶(DNMT3A)基因突变的骨髓增生异常综合征患者的疗效。方法:回顾性分析2015年1月至2018年12月接受地西他滨治疗的59例初诊骨髓增生异常综合征患者的临床特征及其应用地西他滨治疗的反应。根据基因突变情况将患者分为2组:伴DNMT3A基因突变(DNMT3A^+)27例,不伴DNMT3A基因突变(DNMT3A^-)32例。2组患者均治疗4个疗程,比较不同组的疗效及患者生存情况。结果:DNMT3A^+组患者中位年龄为56.2(37-81)岁,与DNMT3A^-组差异无统计学意义(P>0.05);WBC中位数为4.67(0.78-201.4)×10^9/L,Hb中位数为81(46-149)g/L,血小板中位数为85(43-562)×10^9/L,2组比较均无统计学差异(P>0.05)。DNMT3A^+患者对地西他滨总体反应率(ORR)达70.37%,完全缓解(CR)率为40.74%;DNMT3A^-组ORR、CR率分别为40.63%和21.88%,2组总体反应率(ORR)相比有统计学差异(P=0.035),2组完全缓解(CR)率无统计学差异(P=0.159)。2组患者应用地西他滨治疗的不良反应类似。59例患者中,共有21例患者伴有TP53突变,TP53+/DNMT3A^+组(13例)与TP53+/DNMT3A^-组(8例)的ORR及CR率比较差异均无统计学意义(P值分别为0.585、0.353)。DNMT3A^+MDS组总生存期(29.1±13.4个月)高于DNMT3A^-MDS组的总生存期(27.8±14.4个月),但2组比较无统计学意义(P=0.475)。结论:地西他滨治疗伴DNA甲基转移酶(DNMT3A)基因突变的骨髓增生异常综合征患者是有效且安全的,但未显示更好的总生存优势。

Objective:To study therapeutic efficacy and side effects of single decitabine for DNMT3A^+myelodysplastic syndrome(MDS)patients.Methods:The clinical characteristics,efficacy and side effects of 59 myelodysplastic syndrome patients received the decitabine therapy in our center from January 2015 to December 2018 were retrospectively analyzed.Based on gene mutations,these patients were divided into 2 groups:DNMT3A^+MDS patients(n=27)and DNMT3A^-MDS patients(n=32).All patients in two groups were treated with decitabine for 4 circles.The efficacy and side effects in the two groups were compared.Results:The median age of patients in DNMT3A^+MDS group was 56.2(37-81)which was no statistic difference from DNMT3A^-MDS group.And there was no statistical difference including age,white blood cells,hemoglobin and platelet count between the two groups(P>0.05).The ORR and complete response(CR)rate of DNMT3A^+group were 70.37%and 40.74%,the ORR and CR rate of DNMT3A^-group were 40.63%and 21.88%respectively.Significant differences were observed in ORR rate(P=0.035)between two groups.However,significant differences did not found in CR rate(P=0.159)between two groups,The similar adverse reaction was observed in DNMT3A^+and DNMT3A^-MDS patients.Among the 59 patients,21 patients showed TP53+mutation.DNMT3A^+/TP53+MDS patients(n=13)had similar ORR and CR compared with the DNMT3A^-/TP53+MDS patients(n=8)(P>0.05).The overall survival(OS)in DNMT3A^+MDS group and DNMT3A^-MDS group were 29.1±13.4 months and 27.8±14.4 months,respectively,no significant differences between two groups were observed(P=0.475).Conclusion:Decitabine treatment is an effective and safe for DNMT3A^+MDS patients,but not shows better survival advantage.