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

• Published in: Blood cancer journal (New York) 2021-06, Vol.11 (6), p.109-109, Article 109
• Main Authors: Kim, Hee-Je, Kim, Yonggoo, Kang, Dain, Kim, Hoon Seok, Lee, Jong-Mi, Kim, Myungshin, Cho, Byung-Sik
• Format: Article
• Language: English
• Subjects: 45/23; 631/67/1990/283/1897; 631/67/69; 692/308/575; 692/699/1541/1990/283/1897; Aged; Allografts; Biomedical and Life Sciences; Biomedicine; Cancer Research; Female; Hematology; Hematopoietic Stem Cell Transplantation; High-Throughput Nucleotide Sequencing; Humans; Leukemia; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - therapy; Male; Middle Aged; Mutation; Neoplasm, Residual; Oncology; Prognosis; Stem cell transplantation; Transplantation Conditioning; Transplants & implants
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-021-00500-9

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.