期刊
BLOOD CANCER JOURNAL
卷 11, 期 6, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41408-021-00500-9
关键词
-
资金
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI18C0480]
Limited studies on NGS-MRD in AML patients after allo-HSCT prompted this research, which found a significant association between persistent mutations detected pre-HSCT and 1 month post-HSCT with post-transplant relapse and overall survival. Detectable mutations in genes associated with clonal hematopoiesis were also predictive of post-transplant relapse. Serial NGS-MRD monitoring was shown to compensate for the limitations of the initial assay performance.
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.
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