Abstract
<title>Abstract</title> <p>The clinical management of T-ALL/LBL remains challenging due to its genetic heterogeneity and variable outcomes. Integrating comprehensive genetic profiling, including CNAs and NGS mutations, is crucial for refining risk stratification.We retrospectively analyzed 66 adult T-ALL/LBL patients diagnosed between 2017 and 2021. Genetic profiling was performed using MLPA to detect key CNAs and NGS gene mutations. Clinical characteristics, OS and EFS were assessed.NGS mutations were identified in 90.9% (60/66) of patients, with NOTCH1 (46.96%), PHF6 (25.76%), and NRAS (18.18%) being the most frequent. MLPA revealed CNAs in 68.3% (41/60) of sequenced patients, with Del10q (22.73%) and Del17q (15.15%) being the most common. Multivariate analyses identified mutations in TET2 and NRAS, along with Del17q, as independent prognostic factors. A novel prognostic model was constructed by assigning one point for each of these risk factors, stratifying patients into low- (0 points), intermediate- (1 point), and high-risk (≥ 2 points) groups. This model significantly discriminated outcomes, with progressively worse OS and EFS across groups (p < 0.05). Subgroup analysis of 41 patients who underwent allogeneic hematopoietic stem cell transplantation confirmed that HSCT failed to improve the poor prognosis of the high-risk group defined by this model.Our study demonstrated the synergistic value of integrating MLPA and NGS for risk stratification in adult T-ALL/LBL.The developed prognostic model, based on TET2, NRAS, and del17q, effectively identifies a very-high-risk patient population with dismal outcomes even after allogeneic HSCT, facilitating early intervention and guiding novel therapeutic strategies.</p>