异基因造血干细胞移植治疗难治/复发急性髓系白血病的疗效及预后因素分析

Clinical Outcomes and Prognostic Factors of Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

目的:探讨异基因造血干细胞移植(allo-HSCT)治疗难治/复发急性髓系白血病(AML)患者的疗效及影响预后的相关因素。方法:回顾性分析2013年12月至2020年6月在我院接受allo-HSCT治疗的80例难治/复发AML患者的临床资料,主要观察患者总体生存(OS)率、无病生存(DFS)率、复发率及移植相关死亡(TRM)率,并分析影响移植预后的危险因素。结果:纳入研究的80例患者移植后均获得造血重建,3年OS、DFS率分别为(48.8±6.3)%和(40.8±6.7)%,3年累积复发率为33.8%(95%CI:0.254-0.449),3年累积TRM率为15.0%(95%CI:0.114-0.198)。单因素分析结果显示,移植前未达完全缓解、合并DNMT3A R882突变和移植后合并II-IV度急性移植物抗宿主病(aGVHD)是影响患者OS和DFS的预后不良因素。多因素分析结果显示,合并DNMT3A R882突变和移植后合并II-IV度aGVHD是影响患者OS(HR=0.253,95%CI:0.092-0.695,P=0.008;HR=5.681,95%CI:2.101-15.361,P=0.001)和DFS(HR=0.200,95%CI:0.071-0.569,P=0.003;HR=7.117,95%CI:2.556-19.818,P<0.001)的独立危险因素。细胞遗传学高危组患者的复发风险为71.4%(95%CI:0.610-0.836),较中危组患者的23.3%(95%CI:0.147-0.370)和低危组患者的23.5%(95%CI:0.127-0.437)明显增加(P=0.006)。结论:Allo-HSCT是挽救性治疗难治/复发AML患者的有效手段,合并DNMT3A R882突变和移植后合并II-IV度aGVHD是影响难治/复发AML患者移植预后的独立危险因素。

Objective: To investigate the clinical outcomes and prognostic factors of refractory/relapsed acute myeloid leukemia(AML) patients who received allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: The clinical data of 80 refractory/relapsed AML patients who received allo-HSCT from December 2013 to June 2020 were retrospectively analyzed, including the overall survival(OS) rate, disease-free survival(DFS) rate, relapse rate, incidence of transplant-related mortality(TRM), and the related risk factors were explored. Results: Hematopoietic reconstitution was obtained in all 80 patients after transplantation, the 3-year OS and DFS rates were(48.8±6.3)% and(40.8±6.7)%,respectively. The 3-year cumulative incidence of relapse and TRM were 33.8%(95%CI: 0.254-0.449) and 15.0%(95%CI:0.114-0.198), respectively. Univariate analysis showed that non-remission(NR) status before transplantation, DNMT3A R882 mutations and grade II-IV acute graft-versus-host disease(aGVHD) had negative effects on OS and DFS.Multivariate analysis indicated that the DNMT3A R882 mutations and grade II-IV aGVHD were independent risk factors for OS(HR=0.253, 95%CI: 0.092-0.695, P=0.008;HR=5.681, 95%CI: 2.101-15.361, P=0.001) and DFS(HR=0.200,95%CI: 0.071-0.569, P=0.003;HR=7.117, 95%CI: 2.556-19.818, P<0.001). The 3-year cumulative incidence of relapse was 71.4%(95%CI: 0.610-0.836) in genetic high-risk group, which was higher than 23.3%(95%CI: 0.147-0.370) in intermediate-risk group and 23.5%(95%CI: 0.127-0.437) in favorable-risk group(P=0.006). Conclusion: Allo-HSCT is an effective and safe choice for refractory/relapsed AML patients. DNMT3A R882 mutations and grade II-IV aGVHD are negative prognostic factors of allo-HSCT for refractory/relapsed AML patients.