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Prognostic value of measurable residual disease monitoring by next-generation sequencing before and after allogeneic hematopoietic cell transplantation in acute myeloid leukemia
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2021-06-04 , DOI: 10.1038/s41408-021-00500-9
Hee-Je Kim 1, 2 , Yonggoo Kim 3, 4 , Dain Kang 3 , Hoon Seok Kim 3, 4 , Jong-Mi Lee 3, 4 , Myungshin Kim 3, 4 , Byung-Sik Cho 1, 2
Affiliation  

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.



中文翻译:

二代测序对急性髓系白血病异基因造血细胞移植前后可测量残留病灶监测的预后价值

鉴于对异基因造血干细胞移植 (allo-HSCT) 后急性髓性白血病 (AML) 患者的下一代基于测序的可测量残留病 (NGS-MRD) 的研究有限,我们在异基因造血干细胞移植 (allo-HSCT) 前后纵向收集了两个样本独立的前瞻性队列(n = 132)并调查了基于扩增子的 NGS 评估的预后影响。在 HSCT 前(43%)和 HSCT 后 1 个月(HSCT-1m 后,20%)检测到持续突变。HSCT 前和 HSCT-1m 后的所有持续突变都与移植后复发和较差的总体生存率显着相关。从 HSCT 前到 HSCT-1m 后 MRD 状态的变化表明复发和死亡的风险更高。与克隆造血相关的基因中孤立的可检测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调节强度(HSCT 前用于清髓性调节,HSCT-1m 后用于降低强度调节)。连续 NGS-MRD 监测显示,在 allo-HSCT 后从未复发的患者中,HSCT 前和 HSCT-1m 后的大多数残留克隆消失了。通过 NGS-MRD 分析检测到突变克隆在明显复发之前的再次出现。总之,NGS-MRD 检测在 HSCT 前和 HSCT-1m 后都具有预后价值,无论突变类型如何,取决于条件强度。连续 NGS-MRD 监测可以弥补 NGS-MRD 检测的有限性能。

更新日期:2021-06-04
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