阿扎胞苷用于急性髓系白血病移植后维持治疗的临床疗效分析

Efficacy of maintenance therapy with azacitidine for acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

目的:探讨阿扎胞苷用于急性髓系白血病(acute myeloid leukemia,AML)患者异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后维持治疗的疗效以及安全性。方法:回顾性分析2018年11月至2021年8月在空军军医大学第二附属医院造血干细胞移植中心接受allo-HSCT且在移植后使用阿扎胞苷维持治疗的30例AML患者的临床资料,观察患者移植后的微小残留病(minimal residual disease,MRD)转阴情况及移植物抗宿主病(graft-versus-host disease,GVHD)的发生情况,采用Kaplan-Meier法计算总体生存(overall survival,OS)率、无病生存(disease-free survival,DFS)率及累积复发率,并评估该方案的安全性。结果:83.33%(25/30)的患者完成了4个周期的维持治疗,36.67%(11/30)的患者完成了全部6个周期的维持治疗。使用阿扎胞苷维持治疗后10例MRD阳性患者中的9例转为阴性,总体转阴率达90%。随访至2021年11月30日,30例患者的中位生存期为(33.7±1.8)个月,3年OS率为(83.2±9.9)%,3年DFS率为(81.3±9.4)%。至随访截止,共4例(13.33%)患者复发,3年累积复发率为(18.7±9.4)%。治疗中23.33%(7/30)的患者出现Ⅲ~Ⅳ度骨髓抑制。2例患者皮肤慢性移植物抗宿主病(chronic graft-versus-host disease,cGVHD)不同程度减轻,1例患者肝脏cGVHD加重,无患者出现新发GVHD的现象。结论:应用阿扎胞苷进行AML患者allo-HSCT后的维持治疗,可降低复发率,改善患者生存期,且安全性和耐受性良好,不增加患者GVHD的发生率。

Objective:To investigate the efficacy and safety of maintenance therapy with azacitidine for acute myeloid leukemia(AML)patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:The clinical data of 30 AML patients who received maintenance therapy with azacitidine(after allo-HSCT in The Second Affiliated Hospital of Air Force Military Medical University from November 2018 to August 2021)were retrospectively analyzed.The minimal residual disease(MRD)status of the patients after allo-HSCT and the incidence of graft-versus-host disease(GVHD)were monitored.The overall survival(OS)rate,disease-free survival(DFS)rate,and the cumulative incidence of relapse were estimated via Kaplan-Meier methodology and the safety of the treatment protocol was analyzed.Results:83.33%(25/30)patients received at least four cycles of azacitidine maintenance therapy,while 36.67%(11/30)patients received all six cycles of azacitidine maintenance therapy.The MRD status of 10 patients was positive before maintenance therapy,and the MRD status of 9 patients turned negative after maintenance therapy.The overall negative conversion rate was 90%.Following up until November 30,2021,the median OS time of the 30 patients was(33.7±1.8)months,the three-year OS rate was(83.2±9.9)%,and the three-year DFS rate was(81.3±9.4)%.Until the end of follow-up time,four patients relapsed,and the three-year cumulative incidence of relapse was(18.7±9.4)%.The incidence of grade 3/4 hematological toxicities was 23.33%(7/30).Chronic GVHD(cGVHD)of skin was alleviated in two of the patients,and cGVHD of the liver was aggravated in one of the patients.No new onset of GVHD occurred in any of the patients.Conclusions:Maintenance therapy with azacitidine for AML patients after allo-HSCT could reduce the relapse rate and improve the survival of patients.The therapy also has low hematologic toxicity and exhibits no increases in the incidence of GVHD.