阿扎胞苷联合低剂量HAG方案治疗新诊断不适合强化疗老年急性髓系白血病患者的效果及安全性

Efficacy and safety of azacytidine combined with low-dose HAG regimen in treatment of newly diagnosed elderly acute myeloid leukemia patients ineligible for intensive chemotherapy

目的:探讨阿扎胞苷联合低剂量HAG方案治疗新诊断不适合强化疗老年急性髓系白血病(AML)患者的效果及安全性。方法:前瞻性纳入深圳市第二人民医院2019年7月至2021年9月收治的18例新诊断不适合强化疗的老年AML患者,非随机分为阿扎胞苷联合HAG方案(AZA-HAG)组9例和地西他滨联合HAG方案(DEC-HAG)组9例。研究主要终点为总体有效[完全缓解(CR)+部分缓解],次要终点包括CR+伴血细胞计数不完全恢复的完全缓解(CRi)、总生存(OS)和药物安全性。采用Kaplan-Meier法分析OS。结果:18例患者中位年龄为67岁(60~77岁),其中8例为预后高危组。AZA-HAG组治疗1个疗程后总体有效及CR+CRi均7例,DEC-HAG组均8例,两组差异均无统计学意义(均P=1.000)。两组CR+CRi中位持续时间均为7个月,中位OS时间均为12个月;两组OS差异无统计学意义(χ^(2)=0.02,P=0.895)。AZA-HAG组1例TP53突变和1例ASXL1+RUNX1突变患者均获得CR,1例NPM1野生型合并FLT3-ITD、ASXL1突变患者未缓解。两组3~4级血液学不良反应发生率差异均无统计学意义(均P>0.05)。结论:阿扎胞苷联合低剂量HAG方案治疗新诊断不适合强化疗老年AML患者的效果及远期生存较理想,不良反应可耐受。

Objective:To evaluate the efficacy and safety of azacitidine combined with HAG regimen in the treatment of newly diagnosed elderly acute myeloid leukemia(AML)patients ineligible for intensive chemotherapy.Methods:Eighteen newly diagnosed elderly AML patients ineligible for intensive chemotherapy from July 2019 to September 2021 in the Second People's Hospital of Shenzhen were prospectively enrolled in this study.They were non-randomly divided into azacitidine combined with HAG regimen(AZA-HAG)group(9 cases)and decitabine combined with HAG regimen(DEC-HAG)group(9 cases).The primary endpoint of the study was overall response[complete remission(CR)+partial remission],and the secondary endpoints included CR+complete remission with incomplete count recovery(CRi),overall survival(OS)and drug safety.Kaplan-Meier method was used to analyze the OS.Results:The median age of 18 patients was 67 years old(60-77 years old),and 8 of them were in high-risk group.After one course of treatment,the overall response and CR+CRi were observed in 7 of 9 patients in AZA-HAG group,and they were observed in 8 of 9 patients in DEC-HAG group,and there was no significant difference between the two groups(both P=1.000).The median duration of CR+CRi was 7 months in both groups,and the median OS time was 12 months in both groups;there was no significant difference in OS between the two groups(χ^(2)=0.02,P=0.895).In AZA-HAG group,1 patient with TP53 mutation and 1 patient with ASXL1+RUNX1 mutation acquired CR,and 1 patient with NPM1 wild-type combined with FLT3-ITD and ASXL1 mutation did not respond.There was no significant difference in the incidence of grade 3-4 hematological adverse reactions between the two groups(all P<0.05).Conclusions:Azacitidine combined with low-dose HAG regimen in the treatment of newly diagnosed elderly AML patients ineligible for intensive chemotherapy has satisfactory efficacy and long-term survival,and the adverse reactions can be tolerated.