异基因造血干细胞移植后巨细胞病毒再活化对急性髓系白血病复发和生存的影响

Impact of cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation on relapse and survival in patients with acute myeloid leukemia

目的:探讨巨细胞病毒(CMV)再活化对于完全缓解期行异基因造血干细胞移植术(allo-HSCT)的急性髓系白血病(AML)患者复发和生存的影响。方法:对106例于完全缓解期行allo-HSCT的成人AML患者的资料进行回顾性分析,包括移植术后CMV再活化的发生情况和影响因素,以及CMV再活化对于复发和生存的影响。结果:67.0%(71/106)的患者在移植后12个月内出现了CMV再活化,中位时间为移植后46(1～117)d。HLA不全相合和预处理应用兔抗人胸腺细胞免疫球蛋白(ATG)是移植后CMV再活化的影响因素。106例患者移植后的中位随访时间为36(1～171)个月,19例患者移植后出现复发,中位复发时间为4.5(2～38)个月,3年累积复发率为17.8%。单因素分析显示,Ⅱ～Ⅳ度急性移植物抗宿主病和慢性移植物抗宿主病的发生可降低患者的复发率,而CMV再活化对于移植后的复发率无明显影响。106例患者的3年总生存率(OS)为77.2%,无病生存率(DFS)为76.0%。单因素分析显示,年龄>40岁和移植后CMV再活化影响患者的OS,但不影响DFS。Cox多因素回归分析显示,移植后CMV再活化是影响患者3年OS的独立危险因素。结论:HLA不全相合和预处理过程中应用ATG是导致移植后CMV再活化的危险因素,而CMV再活化对于完全缓解期AML移植后的复发并没有影响,但仍是影响此类患者生存的独立危险因素。

Objective:To investigate the impact of cytomegalovirus(CMV)reactivation on relapse and survival in acute myeloid leukemia(AML)patients undergoing allogeneic hematopoietic stem cell transplantation(alloHSCT)in complete remission(CR).Method:The clinical data from 106 adult AML patients undergoing alloHSCT in CR were retrospectively analyzed.The occurrence and risk factors of CMV reactivation after transplantation,as well as the impact of CMV reactivation on the relapse and survival of AML patients were statistically analyzed.Result:CMV reactivation occurred in 67.0%(71/106)patients within 1 year after transplantation.Median time to initial CMV reactivation was 46 days(range,1-117 days).HLA mismatch and administration of anti-thymoglobulin(ATG)in conditioning regimen were associated with CMV reactivation after transplantation.The median time of follow-up in 106 patients was 36 months(range,1-171 months)after transplantation.19 patients relapsed at a median time of 4.5 months(range,2-38 months).The 3-year cumulative recurrence rate of AML was17.8%.The onset ofⅡ-Ⅳ acute graft-versus-host disease and chronic graft-versus-host disease had preventive effect on AML relapse,while CMV reactivation had no such effect.The 3-year overall survival(OS)of 106 patients was 77.2%,and the disease-free survival(DFS)was 76.0%.Age>40 years old and CMV reactivation decreased OS but not DFS.Cox multivariate regression analysis showed that CMV reactivation after transplantation was an independent risk factor for 3-year OS.Conclusion:HLA mismatch and administration of ATG in conditioning regimen are the risk factors for CMV reactivation,and this reactivation remains a risk factor for poor posttransplantation outcomes and has no preventive effect on AML relapse for patients undergoing allo-HSCT in CR.