TP53 mutations predict poor prognosis in diffuse large B-cell lymphoma: A single-center study
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Evidence linking TP53 mutations to survival outcome and treatment efficacy in diffuse large B-cell lymphoma (DLBCL) remains limited. In this retrospective cohort of 436 newly diagnosed DLBCL patients, TP53 mutations were independent prognostic factors for poor overall survival (OS) and progression-free survival (PFS) (both P < 0.001). Compared with TP53 wild-type patients, those with TP53 mutations had poorer response to R-CHOP and higher rates of relapsed/refractory disease ( P = 0.001). R-CHOP combined with azacitidine significantly improved efficacy, showing higher complete remission (CR) (91.67% vs R-CHOP, P = 0.023) and overall response (OR) rates (100% vs R-CHOP, P = 0.029). In subgroup analysis, TP53 mutations were associated with unfavorable survival in GCB subtypes, but not in non-GCB subtypes, and it also indicates adverse prognosis in double-expressor lymphomas(DEL). Survival outcomes were worse in patients with Variant Allele Frequency (VAF) ≥ 60% and DNA-binding domains (DBD) mutations (particularly exons 5 and 8). No survival difference were observed between single-site and multiple-site mutations, nor gain-of-function (GOF) and loss-of-function (LOF) mutations. In addition, we adapted a p53 immunohistochemical classification from ovarian/endometrial cancer to enhance TP53 mutations prediction: overexpression (> 80%) or complete absence (< 1%) as high-risk, and heterogeneity (1%-80%) as low-risk. This approach achieved 70.83% sensitivity and 97.35% specificity, with specificity surpassed conventional ≥ 50% cutoff ( P < 0.001), indicating enhanced precision in predicting TP53 mutation risk.
