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

Abstract

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.

Molecular Minimal Residual Disease Detection in Acute Myeloid Leukemia

“…The presence of any persistent mutation was associated with a higher risk of relapse and decreased OS. In contrast to previous findings, persistence of isolated DTA mutations in CR was also associated with post-transplant relapse [ 61 ].…”

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML)

“…Genomic DNA was extracted from the BM aspirates with the QIAamp DNA Mini Kit (Qiagen, Hamburg, Germany). For detection of genetic mutation, next-generation sequencing (NGS) was performed using a customized St. Mary’s customized NGS panel for acute leukemia (SM acute leukemia panel) including 67 genes, 33 , 34 while the detection of FLT3 -ITD mutation, polymerase chain reaction (PCR) for fragment analysis was performed using a modified protocol as previously described. 35 – 38 The mutation results used in this study almost ( n = 98, 68.5%) relied on initial NGS results except for patients with available NGS results at relapse.…”

Spectrum of Genetic Mutations in Korean Pediatric Acute Lymphoblastic Leukemia

“…NGS was performed using a St. Mary’s customized NGS panel for acute leukemia, i.e., the “SM Acute leukemia panel”. Ion AmpliSeq Technology was used to amplify 67 genes ( Supplementary Table S1 ) using an Ion Chef™ system and an Ion S5 XL Sequencer (all from Thermo Fisher Scientific, Waltham, MA, USA) [ 20 ]. Sequenced reads were mapped to the human reference genome (hg19, Genome Reference Consortium, February 2009).…”