Measurable residual disease detected by next-generation sequencing in T-cell acute lymphoblastic leukemia

Abstract

The clinical utility of measurable residual disease monitoring based on next-generation sequencing in T-cell acute lymphoblastic leukemia remains incompletely defined. Here we show the prognostic value of tracking clonal T-cell receptor gene rearrangements by next-generation sequencing in pediatric patients with T-cell acute lymphoblastic leukemia. Among the 101 patients with trackable clones, measurable residual disease levels at the end of consolidation strongly stratify 4-year event-free survival: 81.6% ± 5.6% for disease levels below 0.0001%, 61.9% ± 11.8% for 0.0001-0.1%, and 45.1% ± 12.1% for levels ≥ 0.1% (P = 0.004). Both T-cell receptor beta and gamma/delta rearrangements demonstrate prognostic significance. Notably, patients with multiparameter flow cytometry-negative but next-generation sequencing-positive measurable residual disease at the end of consolidation have significantly lower 4-year event-free survival compared to those achieving double-negative status (60.8% ± 9.4% vs. 84.9% ± 5.3%, P = 0.038). In conclusion, measurable residual disease monitoring by next-generation sequencing provides superior sensitivity and important clinical value, offering a potential strategy for precise risk stratification in T-cell acute lymphoblastic leukemia. The clinical value of next-generation sequencing for measurable residual disease (NGS-MRD) monitoring in T-cell acute lymphoblastic leukemia remains to be fully established. Tracking TCR rearrangements in pediatric patients, this study shows that NGS-MRD serves as a useful method to stratify outcomes and identifies high-risk cases.