Department of Internal Medicine, King Edward Medical University, Lahore, Pakistan.
Department of Internal Medicine, Khyber Medical College Peshawar, Peshawar, Pakistan.
Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):e865-e875. doi: 10.1016/j.clml.2021.06.012. Epub 2021 Jun 24.
Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma arising from thymic B-cells having clinicopathologic features distinct from systemic diffuse large B-cell lymphoma (DLBCL). PMBCL comprises 2% to 4% of all non-Hodgkin lymphomas (NHL), 7% of DLBCL and seen predominantly in young females with a median age of 35 years at diagnosis. The annual incidence of PMBCL is 0.4 per million with a 5-year survival rate exceeding 70% with improving supportive care and genetic characterization of the disease. Pathogenesis involves dysregulation of Janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor-kB (NF-kB) pathways and amplification of the 9p24.1 region of chromosome 9. PMBCL patients have a prolonged life expectancy necessitating the need for treatment approaches that are based on maximizing cure with minimal long-term toxicity. Due to rarity and its recognition as a distinct entity, therapeutic decisions are guided by clinical presentation, clinician and center experience, and analysis of patients with PMBCL within DLBCL registries. Historically R-CHOP has been the usual first line treatment for PMBCL followed by involved site radiotherapy (ISRT), however clinical practice varies across centers with emerging consensus to avoid upfront RT by utilizing dose intense regimens (DA-EPOCH-R) in younger and fit patients. Prognosis of relapsed refractory PMBCL not responding to salvage chemotherapy is dismal, however there are many emerging options including Brentuximab Vedotin, immune check point inhibitors and chimeric antigen receptor T-cell therapy. In this article, we focus on the pathogenesis, current and evolving treatments, and provide recommendations for optimal management of patients with PMBCL.
原发性纵隔大 B 细胞淋巴瘤（PMBCL）是一种源自胸腺 B 细胞的侵袭性 B 细胞淋巴瘤，其临床病理特征与系统性弥漫性大 B 细胞淋巴瘤（DLBCL）不同。PMBCL 占所有非霍奇金淋巴瘤（NHL）的 2%至 4%，占 DLBCL 的 7%，主要见于年轻女性，诊断时的中位年龄为 35 岁。PMBCL 的年发病率为每百万 0.4 例，随着支持性护理的改善和疾病的遗传特征分析，5 年生存率超过 70%。发病机制涉及 Janus 激酶-信号转导和转录激活因子（JAK-STAT）、核因子-kB（NF-kB）途径的失调和染色体 9 的 9p24.1 区域的扩增。PMBCL 患者的预期寿命延长，因此需要采用基于最大限度治愈和最小化长期毒性的治疗方法。由于罕见性及其作为一种独特实体的认识，治疗决策取决于临床表现、临床医生和中心经验，以及对 DLBCL 登记处中 PMBCL 患者的分析。历史上，R-CHOP 一直是 PMBCL 的常规一线治疗方法，随后是受累部位放疗（ISRT），然而，各中心的临床实践存在差异，新兴共识是通过在年轻和健康的患者中使用剂量密集型方案（DA-EPOCH-R）避免 upfront RT。对挽救化疗无反应的复发性难治性 PMBCL 的预后不佳，然而，有许多新的选择，包括 Brentuximab Vedotin、免疫检查点抑制剂和嵌合抗原受体 T 细胞疗法。本文重点介绍了 PMBCL 的发病机制、当前和不断发展的治疗方法，并为 PMBCL 患者的最佳管理提供了建议。
