Prognostic value of dynamic minimal residual disease monitoring for adolescent and adult T-lymphoblastic leukemia/lymphoma.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a high-risk malignancy with poor outcomes due to frequent relapse. The prognostic role of minimal residual disease (MRD) dynamic monitoring in adult T-ALL/LBL needs further validation across chemotherapy and transplantation phases. This large-scale study aimed to assess multi-timepoint MRD as a predictive biomarker, and integrated risk factors in adult T-ALL/LBL. 348 T-ALL/LBL patients treated with induction/consolidation chemotherapy ± allogeneic hematopoietic stem cell transplantation (allo-HSCT) were involved. MRD was assessed via multiparameter flow cytometry (MFC) at four landmark timepoints: post-induction (EOI-MRD), post-consolidation (EOC-MRD), pre-HSCT (pre-MRD), and post-HSCT (post-MRD). The prognostic value of routine clinical and laboratory variables was analyzed. The cohort exhibited 10-year OS and EFS rates of 35.0% and 28.2%, respectively. Adverse prognostic factors included thrombocytopenia (PLT ≤ 90 × 10⁹/L; p = 0.0195), elevated LDH (> 600 IU/L; p = 0.0338), cerebrospinal fluid (CSF) infiltration (p = 0.0012), and induction failure (p = 0.0237). HSCT improved outcomes (median OS: 24 vs. 17 months; p = 0.0007), especially in relapsed/refractory (R/R) patients (5-year OS: 40% vs. < 20%; p = 0.0042). MRD positivity predicted inferior survival at all timepoints (EOI-MRD: p = 0.0255; pre-HSCT: p = 0.0156; post-HSCT: p < 0.0001, 100% relapse if positive). Chemotherapy-only patients with sustained MRD negativity had a reduced relapse rate (p = 0.0090) and superior OS (p = 0.0001). In conclusion, dynamic MRD monitoring (pre-/post-HSCT and during chemotherapy) is prognostic in adult T-ALL/LBL. Combined with variables including LDH and MRD kinetics enables precision prognostication and guides therapeutic decision-making, including early HSCT for persistent MRD-positive cases.