Next-Generation Sequencing-Based MRD in Adults with ALL Undergoing Hematopoietic Cell Transplantation. Blood advances Liang, E. C., Dekker, S. E., Sabile, J. M., Torelli, S., Zhang, A., Miller, K., Shiraz, P., Hayes-Lattin, B., Leonard, J. T., Muffly, L. 2023


Measurable residual disease (MRD) is an adverse prognostic factor in adult acute lymphoblastic leukemia (ALL) patients undergoing hematopoietic cell transplantation (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10-6, but the prognostic value of NGS-based MRD in adult ALL patients undergoing HCT remains minimally studied. To evaluate the prognostic value of NGS-based MRD in adult ALL patients undergoing HCT. Patients with ALL aged =18 years old who underwent allogeneic HCT at Stanford University or Oregon Health & Science University between January 2014-April 2021 and who were evaluated for MRD using the NGS-based clonoSEQ assay were included in this study. MRD was assessed pre-HCT (MRDpre) and for up to 1 year post-HCT (MRDpost). Patients were followed for leukemia relapse and survival for up to 2 years post-HCT. 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10-4 (HR 3.56, 95% CI, 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR 4.60, 95% CI, 3.01-7.02). In exploratory analyses limited to B-cell ALL patients, detection of post-HCT IgH MRD clonotypes, rather than non-IgH MRD clonotypes, were associated with relapse. In this analysis across two large transplant centers, we found that detection of MRD by NGS at a level of 10-6 offers significant prognostic value in adults with ALL undergoing HCT.

View details for DOI 10.1182/bloodadvances.2023009856

View details for PubMedID 37196642