异基因造血干细胞移植治疗54例骨髓增生异常综合征转化急性髓系白血病的疗效和预后分析

Clinical efficacy of allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome-evolved acute myeloid leukemia

目的评估异基因造血干细胞移植(allo-HSCT)治疗骨髓增生异常综合征转化急性髓系白血病(MDS-AML)的疗效。方法收集2018年1月至2022年8月在中国医学科学院血液病医院接受allo-HSCT的MDS-AML患者,对其临床资料进行回顾性分析。结果54例患者纳入研究,男26例,女28例,中位年龄46(9~57)岁。53例患者获得粒系造血重建。中位随访597(15~1934)d。移植后1年总生存(OS)率、无病生存(DFS)率分别为(75.8±5.8)%、(72.1±6.1)%,累积复发率(CIR)为(12.7±4.9)%,非复发死亡率(NRM)为(17.1±5.2)%;移植后3年OS率、DFS率分别为(57.8±7.5)%、(58.1±7.2)%,CIR为(23.2±6.6)%,NRM为(23.7±6.6)%。急性移植物抗宿主病(aGVHD)累积发生率为(57.5±6.9)%,慢性移植物抗宿主病(cGVHD)累积发生率为(48.4±7.7)%。单因素分析显示,移植前造血干细胞移植合并症指数(HCT-CI)评分≥2分、造血植入时骨髓微小残留病(MRD)阳性、发生Ⅲ/Ⅳ度aGVHD、发生细菌/真菌感染以及未发生cGVHD是影响OS的不良因素(P<0.05)。多因素因素分析显示,HCT-CI评分≥2分(P=0.001,HR=6.981,95%CI 2.186~22.300)、造血植入时骨髓MRD阳性(P=0.010,HR=6.719,95%CI 572~28.711)、发生Ⅲ/Ⅳ度aGVHD(P=0.026,HR=3.386,95%CI 1.158~9.901)以及cGVHD(P=0.006,HR=0.151,95%CI 0.039~0.581)是影响OS的独立危险因素。结论对于高复发风险的MDS-AML患者,可考虑早期进行allo-HSCT,移植后加强并发症的处理以及在患者病情允许下尽早开始维持治疗。

Objective The outcomes of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for myelodysplastic syndromes-evolved acute myeloid leukemia(MDS-AML)were explored.Methods A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022.The clinical effects after transplantation were observed,and the related risk factors influencing prognosis were explored.Results Of the total 54 patients,26 males,28 females,and 53 patients achieved hematopoietic reconstruction.After a median follow-up of 597(15-1934)days,the 1 year overall survival(OS)rate,disease-free survival(DFS)rate,relapse rate(CIR)and non-relapse mortality(NRM)rate were 75.8%±5.8%,72.1%±6.1%,12.7%±4.9%,and 17.1%±5.2%,respectively.The 3 year estimated OS,DFS,CIR,and NRM rates were 57.8%±7.5%,58.1%±7.2%,23.2%±6.6%,and 23.7%±6.6%,respectively.The cumulative incidence of acute graft-versus-host disease(aGVHD)was 57.5%±6.9%,and the cumulative incidence of chronic graft-versus-host disease(cGVHD)was 48.4%±7.7%.Hematopoietic cell transplantation comorbidity index(HCT-CI)before transplantation was≥2,minimal residual disease(MRD)was positive on the day of reconstitution,gradeⅢ/ⅣaGVHD,bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS(P<0.05).COX regression model for multivariate analysis showed that HCT-CI score before transplantation,bone marrow MRD on the day of response,gradeⅢorⅣaGVHD,and cGVHD after transplantation were the independent adverse factors for OS(P=0.001,HR=6.981,95%CI 2.186-22.300;P=0.010,HR=6.719,95%CI 1.572-28.711;P=0.026,HR=3.386,95%CI 1.158-9.901;P=0.006,HR=0.151,95%CI 0.039-0.581).Conclusion For patients with MDS-AML and high risk of relapse,allogeneic transplantation must be considered as soon as possible.The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.