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The rapidly changing landscape in mature T-cell lymphoma (MTCL) biology and management. ​

文献信息 ​

DOI10.3322/caac.21589
PMID31815293
期刊CA: a cancer journal for clinicians
影响因子232.4
JCR 分区Q1
发表年份2020
被引次数36
关键词管理，新型治疗，外周T细胞淋巴瘤，标准治疗
文献类型Journal Article, Review
ISSN0007-9235
页码47-70
期号70(1)
作者Enrica Marchi, Owen A O'Connor

一句话小结 ​

非霍奇金淋巴瘤（NHL）中的外周T细胞淋巴瘤（PTCL）因其稀有性和异质性，过去30年未能显著改善预后，且大多数治疗方案源自B细胞肿瘤。最近针对PTCL的新药物批准和对其分子机制的深入理解，为开发新型靶向治疗提供了希望，可能会改善该领域患者的治疗效果。

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管理 · 新型治疗 · 外周T细胞淋巴瘤 · 标准治疗

摘要 ​

在非霍奇金淋巴瘤（NHL）患者护理的历史进展中，主要集中在B细胞淋巴瘤患者上。外周T细胞淋巴瘤（PTCL）因其稀有性和异质性，过去20至30年间并未经历同样程度的预后改善。据估计，美国每年约有80,000例NHL和14,000例霍奇金淋巴瘤病例。作为NHL的一个亚组，PTCL占所有NHL病例的6%至10%，因此显得极为稀少。此外，世界卫生组织2017年的分类描述了29种不同的PTCL亚型。这种内在的多样性，加上其稀有性，阻碍了疾病的进展。此外，大多数亚型的预后较B细胞淋巴瘤差，这主要归因于大多数PTCL患者的治疗方案源自B细胞肿瘤，而这是一种截然不同的疾病。实际上，首个获批用于PTCL患者的药物仅在十年前获得批准。近期PTCL药物获批的激增，加上对该疾病分子发病机制的深入理解，刺激了该领域探索新的研究方向，这些研究方向主要基于新型靶向小分子的开发，包括一系列表观遗传修饰剂和生物制剂。人们期待这些进展能够有利地挑战在T细胞恶性肿瘤中使用的化疗方案。

英文摘要 ​

Historical advances in the care of patients with non-Hodgkin lymphoma (NHL) have been restricted largely to patients with B-cell lymphoma. The peripheral T-cell lymphomas (PTCLs), which are rare and heterogeneous in nature, have yet to experience the same degree of improvement in outcome over the past 20 to 30 years. It is estimated that there are approximately 80,000 and 14,000 cases, respectively, of NHL and Hodgkin lymphoma per year in the United States. As a subgroup of NHL, the PTCLs account for 6% to 10% of all cases of NHL, making them exceedingly rare. In addition, the World Health Organization 2017 classification describes 29 distinct subtypes of PTCL. This intrinsic diversity, coupled with its rarity, has stymied progress in the disease. In addition, most subtypes carry an inferior prognosis compared with their B-cell counterparts, an outcome largely attributed to the fact that most treatment paradigms for patients with PTCL have been derived from B-cell neoplasms, a radically different disease. In fact, the first drug ever approved for patients with PTCL was approved only a decade ago. The plethora of recent drug approvals in PTCL, coupled with a deeper understanding of the molecular pathogenesis of the disease, has stimulated the field to pursue new avenues of research that are now largely predicated on the development of novel, targeted small molecules, which include a host of epigenetic modifiers and biologics. There is an expectation these advances may begin to favorably challenge the chemotherapy paradigms that have been used in the T-cell malignancies.

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主要研究问题 ​

  1. 在成熟T细胞淋巴瘤（MTCL）的生物学研究中，哪些新的分子靶向治疗方法显示出最有前景的效果？
  2. 如何评估新药物在不同亚型的周围T细胞淋巴瘤（PTCL）中的疗效与安全性？
  3. 除了化疗之外，还有哪些新兴的治疗策略可能会改善成熟T细胞淋巴瘤患者的预后？
  4. 在PTCL的临床试验中，患者的选择标准是如何影响研究结果的？
  5. 随着对PTCL分子机制理解的加深，未来的研究方向可能会集中在哪些关键领域？

核心洞察 ​

  1. 研究背景和目的
    在过去的20至30年中，非霍奇金淋巴瘤（NHL）的治疗进展主要集中在B细胞淋巴瘤患者身上，而外周T细胞淋巴瘤（PTCL）作为NHL的一种亚型，由于其稀有性和异质性，尚未取得同样程度的改善。美国每年约有80,000例NHL和14,000例霍奇金淋巴瘤病例，而PTCL仅占NHL的6%至10%。此外，世界卫生组织2017年分类中描述了29种不同的PTCL亚型，这种内在的多样性使得疾病的研究和治疗进展受到限制。研究的目的是探讨PTCL的生物学特征和管理策略的快速变化，以期为患者提供更有效的治疗方案。

  2. 主要方法和发现
    该研究回顾了PTCL的最新药物批准和分子病理机制的理解。近年来，针对PTCL的多种新药物获得批准，这些药物主要为靶向小分子，包括多种表观遗传修饰剂和生物制剂。研究表明，现有的PTCL治疗方案大多源自B细胞肿瘤，导致预后相对较差。新药物的开发与对疾病分子机制的深入理解为PTCL的治疗提供了新的研究方向。

  3. 核心结论
    PTCL的治疗正在经历一场快速变化的革命，新的靶向治疗和生物制剂的出现可能会改变传统化疗的治疗模式。随着对PTCL分子病理的深入理解，未来的研究将更加注重个性化和靶向治疗策略，以提高患者的预后和生活质量。

  4. 研究意义和影响
    这项研究的重要性在于，它为PTCL的管理提供了新的视角，强调了靶向治疗在罕见淋巴瘤中的潜力。通过探讨PTCL的生物学特征和治疗进展，研究不仅能够推动该领域的科研进展，还可能改善患者的临床结果。这些发现将激励进一步的研究，以开发更有效的治疗方法，最终提升PTCL患者的生存率和生活质量。

引用本文的文献 ​

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  2. Clinical Remission in a 72-Year-Old Patient with a Massive Primary Cutaneous Peripheral T-Cell Lymphoma-NOS of the Eyelid, Following Combination Chemotherapy with Etoposide Plus COP. - Sabina Iluta;Dragos-Alexandru Termure;Bobe Petrushev;Bogdan Fetica;Mindra-Eugenia Badea;Madalina Moldovan-Lazar;Manuela Lenghel;Csaba Csutak;Andrei Roman;Sergiu Pasca;Alina-Andreea Zimta;Ciprian Jitaru;Ciprian Tomuleasa;Rares-Calin Roman - Diagnostics (Basel, Switzerland) (2020)
  3. All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma. - Maria Christina Cox;Marta Banchi;Sabrina Pelliccia;Arianna Di Napoli;Luigi Marcheselli;Caterina Patti;Paola Anticoli Borza;Roberta Battistini;Francesca Di Gregorio;Paola Orlandi;Guido Bocci - Cancer chemotherapy and pharmacology (2020)
  4. B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974? - Minodora Desmirean;Sebastian Rauch;Ancuta Jurj;Sergiu Pasca;Sabina Iluta;Patric Teodorescu;Cristian Berce;Alina-Andreea Zimta;Cristina Turcas;Adrian-Bogdan Tigu;Cristian Moldovan;Irene Paris;Jakob Steinheber;Cedric Richlitzki;Catalin Constantinescu;Olafur Eysteinn Sigurjonsson;Delia Dima;Bobe Petrushev;Ciprian Tomuleasa - Journal of clinical medicine (2020)
  5. Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma. - Caiqin Xie;Xian Li;Hui Zeng;Wenbin Qian - Experimental hematology & oncology (2020)
  6. Chemotherapy Plus Radiotherapy Versus Chemotherapy Alone for Patients With Peripheral T-Cell Lymphoma, Not Otherwise Specified. - Zegeng Chen;He Huang;Xiaoqian Li;Xiaojie Fang;Zhao Wang;Huangming Hong;Zhihui Zhang;Qingqing Cai;Zhiming Li;Meiting Chen;Yuyi Yao;Fei Pan;Limin Chen;Tongyu Lin - Frontiers in oncology (2021)
  7. A novel lncRNA TCLlnc1 promotes peripheral T cell lymphoma progression through acting as a modular scaffold of HNRNPD and YBX1 complexes. - Ping Zhao;Meng-Meng Ji;Ying Fang;Xiao Li;Hong-Mei Yi;Zi-Xun Yan;Shu Cheng;Peng-Peng Xu;Anne Janin;Chao-Fu Wang;Li Wang;Wei-Li Zhao - Cell death & disease (2021)
  8. Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis. - Jun Du;Dandan Yu;Xinle Han;Lijun Zhu;Zoufang Huang - JAMA network open (2021)
  9. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. - Mehdi Hamadani;Graham P Collins;Paolo F Caimi;Felipe Samaniego;Alexander Spira;Andrew Davies;John Radford;Tobias Menne;Anand Karnad;Jasmine M Zain;Paul Fields;Karin Havenith;Hans G Cruz;Shui He;Joseph Boni;Jay Feingold;Jens Wuerthner;Steven Horwitz - The Lancet. Haematology (2021)
  10. Updates in the Treatment of Peripheral T-Cell Lymphomas. - Khalil Saleh;Jean-Marie Michot;Vincent Ribrag - Journal of experimental pharmacology (2021)

... (26 更多 篇文献)

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