Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics; National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Blood Adv. 2024 Apr 9;8(7):1587-1599. doi: 10.1182/bloodadvances.2023011425.
Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma with clinical and biological heterogeneity. The International Prognostic Index (IPI) shows great prognostic capability in the era of rituximab, but the biological signatures of IPI remain to be discovered. In this study, we analyzed the clinical data in a large cohort of 2592 patients with newly diagnosed DLBCL. Among them, 1233 underwent DNA sequencing for oncogenic mutations, and 487 patients underwent RNA sequencing for lymphoma microenvironment (LME) alterations. Based on IPI scores, patients were categorized into 4 distinct groups, with 5-year overall survival of 41.6%, 55.3%, 71.7%, and 89.7%, respectively. MCD-like subtype was associated with age of >60 years, multiple extranodal involvement, elevated serum lactate dehydrogenase (LDH), and IPI scores ranging from 2 to 5, whereas ST2-like subtype showed an opposite trend. Patients with EZB-like MYC+ and TP53Mut subtypes exhibited poor clinical outcome independent of the IPI; integrating TP53Mut into IPI could better distinguish patients with dismal survival. The EZB-like MYC-, BN2-like, N1-like, and MCD-like subtypes had inferior prognosis in patients with IPI scores of ≥2, indicating necessity for enhanced treatment. Regarding LME categories, the germinal center-like LME was more prevalent in patients with normal LDH and IPI scores of 0 to 1. The mesenchymal LME served as an independent protective factor, whereas the germinal center-like, inflammatory, and depleted LME categories correlated with inferior prognosis for IPI scores of 2 to 5. In summary, our work explored the biological signatures of IPI, thus providing useful rationale for future optimization of the IPI-based treatment strategies with multi-omics information in DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种具有临床和生物学异质性的高度侵袭性淋巴瘤亚型。国际预后指数（IPI）在利妥昔单抗时代显示出了很好的预后能力，但 IPI 的生物学特征仍有待发现。在这项研究中，我们分析了 2592 例新诊断为 DLBCL 的患者的大型队列的临床数据。其中，1233 例患者进行了致癌基因突变的 DNA 测序，487 例患者进行了淋巴瘤微环境（LME）改变的 RNA 测序。根据 IPI 评分，患者被分为 4 个不同的组，5 年总生存率分别为 41.6%、55.3%、71.7%和 89.7%。MCD 样亚型与年龄>60 岁、多个结外累及、血清乳酸脱氢酶（LDH）升高和 IPI 评分为 2 至 5 有关，而 ST2 样亚型则呈相反趋势。EZB 样 MYC+和 TP53Mut 亚型的患者无论 IPI 如何，其临床结局均较差；将 TP53Mut 纳入 IPI 可更好地区分预后不良的患者。EZB 样 MYC-、BN2 样、N1 样和 MCD 样亚型在 IPI 评分≥2 的患者中预后较差，表明需要加强治疗。关于 LME 类别，正常 LDH 和 IPI 评分 0 至 1 的患者中更常见生发中心样 LME。间充质 LME 是一个独立的保护因素，而生发中心样、炎症和耗竭 LME 类别与 IPI 评分 2 至 5 的预后较差相关。总之，我们的工作探讨了 IPI 的生物学特征，为未来利用多组学信息优化基于 IPI 的治疗策略提供了有用的依据。
