Severe toxicity-free survival following acute lymphoblastic leukemia in patients aged 1–45 years: a Danish cohort study
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 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.
Measurable residual disease (MRD) is a critical biomarker for assessing treatment response and guiding therapeutic decisions in acute lymphoblastic leukemia. This study demonstrates that next‑generation sequencing (NGS) of T‑cell receptor rearrangements detects MRD with higher sensitivity than conventional flow cytometry, identifying patients at higher risk of relapse who may benefit from intensified therapy or early transplantation.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.
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