Integrating genomic features for prognosis in Chinese patients with diffuse large B-cell lymphoma following R-CHOP therapy

Diffuse large B-cell lymphoma (DLBCL) exhibits 30-40% rates of relapse or refractory disease after R-CHOP. Identifying patients at risk for treatment failure is essential for planning subsequent therapeutic strategies, including stem cell mobilization or cellular therapy. To identify genomic predictors in Chinese patients, we performed targeted sequencing of tumor and matched oral DNA from 147 cases. Mutations in TP53 (hazard ratio (HR) = 2.78; P = 0.002), SRP72 (HR = 2.79; P = 0.010), MYC (HR = 1.97; P = 0.033), BCL2 (HR = 2.54; P = 0.021), and ASXL2 (HR = 2.20; P = 0.048) were significantly associated with poor PFS. A five-gene mutation risk score combined with baseline lactate dehydrogenase (LDH) and bone marrow tumor cell status improved PFS prediction over the International Prognostic Index (IPI). In addition, TP53 (HR = 4.45; P = 0.003), SRP72 (HR = 4.16; P = 0.014), and MYC (HR = 2.64; P = 0.047) mutations were strongly associated with increased risk of relapse. Integrating the three-gene mutation risk score with baseline LDH showed superior ability to predict relapse compared with the IPI. Combining mutation-derived scores with clinical factors enhanced prognostic discrimination, aiding early identification of patients for stem cell or cellular therapy.