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.