文章：

异基因造血干细胞移植前后通过下一代测序监测可测量残留病灶对急性髓系白血病的预后价值

Prognostic value of measurable residual disease monitoring by next-generation sequencing before and after allogeneic hematopoietic cell transplantation in acute myeloid leukemia

原文发布日期：2021-06-04

DOI: 10.1038/s41408-021-00500-9

类型: Article

开放获取: 是

英文摘要：

Given limited studies on next-generation sequencing-based measurable residual disease (NGS-MRD) in acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), we longitudinally collected samples before and after allo-HSCT from two independent prospective cohorts (n = 132) and investigated the prognostic impact of amplicon-based NGS assessment. Persistent mutations were detected pre-HSCT (43%) and 1 month after HSCT (post-HSCT-1m, 20%). All persistent mutations at both pre-HSCT and post-HSCT-1m were significantly associated with post-transplant relapse and worse overall survival. Changes in MRD status from pre-HSCT to post-HSCT-1m indicated a higher risk for relapse and death. Isolated detectable mutations in genes associated with clonal hematopoiesis were also significant predictors of post-transplant relapse. The optimal time point of NGS-MRD assessment depended on the conditioning intensity (pre-HSCT for myeloablative conditioning and post-HSCT-1m for reduced-intensity conditioning). Serial NGS-MRD monitoring revealed that most residual clones at both pre-HSCT and post-HSCT-1m in patients who never relapsed disappeared after allo-HSCT. Reappearance of mutant clones before overt relapse was detected by the NGS-MRD assay. Taken together, NGS-MRD detection has a prognostic value at both pre-HSCT and post-HSCT-1m, regardless of the mutation type, depending on the conditioning intensity. Serial NGS-MRD monitoring was feasible to compensate for the limited performance of the NGS-MRD assay.
 

摘要翻译： 

鉴于目前针对急性髓系白血病患者异基因造血干细胞移植后基于下一代测序的可测量残留病（NGS-MRD）研究有限，我们纵向收集了两个独立前瞻性队列（n=132）在移植前后的样本，并研究了基于扩增子的NGS评估的预后价值。在移植前（43%）和移植后1个月（20%）均检测到持续存在的突变。无论是移植前还是移植后1个月检测到的持续突变，均与移植后复发及较差的总生存期显著相关。从移植前到移植后1个月期间MRD状态的变化提示更高的复发和死亡风险。与克隆性造血相关基因中检测到的孤立突变也是移植后复发的重要预测因子。NGS-MRD评估的最佳时间点取决于预处理强度（清髓性预处理选择移植前评估，降低强度预处理选择移植后1个月评估）。连续NGS-MRD监测显示，在从未复发的患者中，移植前和移植后1个月残留的克隆大多数在移植后消失。NGS-MRD检测可在明显复发前发现突变克隆的再次出现。综上所述，无论突变类型如何，根据预处理强度不同，NGS-MRD检测在移植前和移植后1个月均具有预后价值。连续的NGS-MRD监测可以有效弥补单次NGS-MRD检测性能的局限性。

原文链接：

Prognostic value of measurable residual disease monitoring by next-generation sequencing before and after allogeneic hematopoietic cell transplantation in acute myeloid leukemia