Objective: To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) . Methods: A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results: Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype (P=0.02, OR=0.39, 95%CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation (P=0.02, OR=0.22, 95%CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95%CI 21.14-30.19) months. HMA response (P=0.036, HR=0.47, 95%CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype (P=0.024, HR=2.14, 95%CI 1.10-4.15) , leukemia transformation (P<0.001, HR=2.839, 95%CI 1.64-4.92) , and TP53 mutation (P=0.012, HR=2.19, 95%CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion: Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.
目的： 研究去甲基化药物（HMA）足疗程治疗骨髓增生异常综合征（MDS）的疗效和安全性。 方法： 纳入来自浙江省45家医院的409例接受了至少连续4个周期的HMA单药起始治疗的MDS患者，评估HMA疗效和安全性。采用Mann-Whitney U或卡方检验比较组间临床资料差异，采用Logistic回归和Cox回归分析疗效与生存的影响因素，采用Kaplan-Meier法进行生存分析。 结果： 409例患者HMA治疗的中位疗程为6（4~25）个疗程。完全缓解（CR）率为33.98%，总缓解率（ORR）为77.02%。多因素分析显示，复杂核型（P=0.02，OR=0.39，95%CI 0.18~0.84）是CR的独立良好影响因素；TP53突变（P=0.02，OR=0.22，95%CI 0.06~0.77）是ORR的独立良好预测因素。患者的中位总生存（OS）时间为25.67（95%CI 21.14~30.19）个月，HMA治疗有反应（P=0.036，HR=0.47，95%CI 0.23~0.95）是OS的独立良好预后因素，而伴有复杂核型（P=0.024，HR=2.14，95%CI 1.10~4.15）、发生白血病转化（P<0.001，HR=2.84，95%CI 1.64~4.92）、TP53突变（P=0.012，HR=2.19，95%CI 1.19~4.07）均是OS的独立不良预后因素。HMA减剂量较标准剂量在疗效和中位OS时间均无显著差异。地西他滨和阿扎胞苷治疗组的CR率、ORR均无显著差异。接受地西他滨治疗患者的中位OS时间长于接受阿扎胞苷治疗患者（29.53个月对20.17个月，P=0.007），但地西他滨组严重骨髓抑制、肺炎发生率高于阿扎胞苷组。 结论： 在患者能够耐受情况下，连续规律地使用适当剂量的HMA，有利于MDS患者最大程度从治疗中获益。.
Keywords: Azacitidine; Decitabine; Hypomethylating agents; Myelodysplastic syndromes; Prognosis.