通过全面的基因组分析，已确定了弥漫性大 B 细胞淋巴瘤 (DLBCL) 的遗传亚型；然而，尚不清楚这是否可以应用于临床实践。我们评估了临床实验室突变分析 (CLMA) 检测到的突变是否可以预测新诊断的 DLBCL/高级别 B 细胞淋巴瘤 (HGBL) 患者的预后。对 2018-2022 年确诊且活检接受 CLMA 并接受 R-CHOP 或 R-EPOCH 的患者进行总体/完全缓解率 (ORR/CRR) 和估计无进展/总体生存 (PFS/OS) 分析。 CLMA 已成功对 117/122 名患者活检 (96%) 进行，中位周转时间为 17 天。中位随访时间为 31.3 个月。在 ≥10% 的活检中检测到的突变中，只有 TP53 与 2 年进展和死亡相关。 36% 的肿瘤中检测到 TP53 突变，TP53 突变患者的 ORR（71% vs 90%，P=0.009）、CRR（55% vs 77%，P=0.01）和 2 年 PFS（57%）显着降低与没有 TP53 突变的患者相比，2 年 OS（70% vs 91%，P=0.001）和复发后中位 OS（6.1 个月 vs 尚未达到，P=0.001）。此外，与非 LOF 突变患者相比，TP53 功能丧失 (LOF) 突变患者的 2 年 PFS/OS 率较低，如果具有高风​​险临床病理特征，则 2 年 PFS 较差或接近较差。通过 CLMA 鉴定的 TP53 突变可以预测新诊断的 DLBCL/HGBL 患者的较差预后。 CLMA 结果可实时用于告知预后和/或确定临床试验候选者。版权所有 © 2023 美国血液学会。

Genetic subgroups of diffuse large B cell lymphoma (DLBCL) have been identified through comprehensive genomic analysis; however, it is unclear if this can be applied in clinical practice. We assessed whether mutations detected by clinical laboratory mutation analysis (CLMA) were predictive of outcomes in patients with newly-diagnosed DLBCL/high grade B cell lymphoma (HGBL). Patients diagnosed from 2018-2022 whose biopsies underwent CLMA and received R-CHOP or R-EPOCH were analyzed for overall/complete response rate (ORR/CRR) and estimated progression free/overall survival (PFS/OS). CLMA was successfully performed in 117/122 patient biopsies (96%) with a median turnaround time of 17 days. Median length of follow-up was 31.3 months. Of mutations detected in ≥10% of biopsies, only TP53 was associated with both progression and death at 2 years. TP53 mutations were detected in 36% of tumors, and patients with TP53 mutations experienced significantly lower ORR (71% vs 90%, P=0.009), CRR (55% vs 77%, P=0.01), 2 year PFS (57% vs 77%, P=0.006), 2 year OS (70% vs 91%, P=0.001) and median OS post-relapse (6.1 months vs not yet reached, P=0.001) as compared to those without TP53 mutations. Furthermore, patients with TP53 loss of function (LOF) mutations experienced lower rates of 2 year PFS/OS than those with non-LOF mutations, and inferior or near-inferior 2 year PFS if harboring high-risk clinicopathologic features. TP53 mutations identified through CLMA can predict for inferior outcomes in patients with newly-diagnosed DLBCL/HGBL. Results of CLMA can be used in real-time to inform prognosis and/or identify candidates for clinical trials.Copyright © 2023 American Society of Hematology.