降低高危骨髓增生异常综合征异基因造血干细胞移植后复发的策略研究

Strategies of lowering relapse after allogeneic hematopoietic stem cell transplantation for high-risk myelodysplastic syndrome

目的从优化预处理和桥接治疗两个角度探索降低高危骨髓增生异常综合征(MDS)异基因造血干细胞移植(allo-HSCT)术后复发的策略。方法对2013年1月至2019年9月于华中科技大学同济医学院附属协和医院血液病研究所接受allo-HSCT的84例高危MDS患者进行回顾性分析。按使用的预处理方案分为:地西他滨强化预处理组49例,BUCY2预处理组35例;按移植前是否接受治疗分为:移植前治疗组34例,未治疗组50例。比较患者造血重建、移植物抗宿主病(GVHD)、复发率、移植相关死亡率(TRM)、存活率的差异。结果地西他滨强化组与BUCY2组相比,造血重建、TRM和急、慢性GVHD发生情况差异无统计学意义;复发率明显低于BUCY2组(18.7%比40.0%,P=0.025),生存显著优于BUCY2组(3年总存活率:71.3%比51.2%,P=0.038;3年无病生存率:65.3%比45.2%,P=0.033)。此外,移植前桥接治疗组复发率明显低于未治疗组(20.7%比38.9%,P=0.035),3年总存活率及无病生存率显著优于未治疗组(71.2%比50.8%,P=0.024;64.7%比45.9%,P=0.044)。结论地西他滨强化BUCY2预处理方案可更好地清除高危MDS患者肿瘤负荷,明显降低移植后复发率,改善生存,是一种较为理想的预处理方案;此外,移植前桥接治疗亦可显著减少移植后复发率,使患者生存获益。故强化预处理及桥接治疗可能是降低此类高危患者移植后复发、改善生存的重要策略,需前瞻性随机对照研究进一步证实。

Objective To explore the strategies of reducing relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with high-risk myelodysplastic syndrome(MDS)from the perspectives of optimizing the conditioning regimen and pre-transplant cytoreductive therapy.Methods A total of 84 patients with high-risk MDS undergoing allo-HSCT between January 2013 and September 2019 were retrospectively analyzed.Based upon preparative regimens,they were divided into two groups of decitabine intensified BUCY2(n=49)and BUCY2 regimen(n=35),based upon whether or not pre-treatment prior to allo-HSCT:cytoredutive treatment(n=34)and none(n=50).Two groups were compared with regards to hematopoietic reconstitution,graft-versus-host disease(GVHD),relapse rate,transplant-related mortality(TRM)and survival.Results No significant inter-group differences existed in hematopoietic reconstitution or acute/chronic GVHD.The relapse rate was significantly lower in decitabine intensified group than that in BUCY2 group(18.7%vs 40.0%,P=0.025).Survival was significantly better in decitabine intensified group than that in BUCY2 group(3-year OS:71.3%vs 51.2%,P=0.038;3-year DFS:65.3%vs 45.2%,P=0.033).Moreover,the incidence of recurrence was markedly lower in pre-transplant treatment group than that in non-treatment group(20.7%vs 38.9%,P=0.035).The inter-group incidence of TRM was not different.Three-year OS/DFS of treatment group were remarkably superior to those of non-treatment group(71.2%vs 50.8%,P=0.024;64.7%vs 45.9%,P=0.044).Conclusions As an optimal conditioning regimen for high-risk MDS,decitabine intensified BUCY2 regimen could better eliminate tumor burden,remarkably lower relapse rate and improve OS after allo-HSCT.In addition,pre-transplant treatment significantly reduces relapse and offers benefit for OS after allo-HSCT.Therefore intensified conditioning regimen and pre-transplant treatment may be promising strategies of reducing relapse and improving survival for high-risk MDS.However,it still needs further confirmation from prospective randomized controlled trials.