Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center , New Haven, CT, USA.
Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center , New Haven, CT, USA.
Expert Rev Hematol. 2020 Nov;13(11):1189-1199. doi: 10.1080/17474086.2020.1839887. Epub 2020 Nov 1.
Essential thrombocythemia (ET) and polycythemia vera (PV) belong to the BCR-ABL1-negative myeloproliferative neoplasms and are characterized by the clonal proliferation of hematopoietic stem and progenitor cells. The contribution of aberrant immune regulation within the bone marrow microenvironment to ET and PV pathogenesis as well as the underlying molecular landscape is becoming increasingly understood.
Authors searched PubMed and conference abstracts in August 2020 for preclinical and clinical studies to provide an overview of the immune pathobiology in ET and PV and the rationale for several novel agents. A discussion of recent clinical trials on interferon and ruxolitinib in ET and PV patients is provided followed by an outline of the future challenges in the field particularly for novel therapeutics and an increasingly individualized, molecularly driven approach to treatment selection. Several novel agents are currently being actively evaluated and are reviewed herein as well.
While hydroxyurea remains the first-line treatment for cytoreduction in most high-risk ET and PV patients, the disease-modifying potential of IFN is promising and could make it a preferred option for selected patients. Advances in molecular testing will enable a more individualized approach to prognostication and treatment selection.
特发性血小板增多症（ET）和真性红细胞增多症（PV）属于 BCR-ABL1 阴性骨髓增殖性肿瘤，其特征是造血干细胞和祖细胞的克隆性增殖。骨髓微环境中异常免疫调节对 ET 和 PV 发病机制以及潜在的分子谱的贡献越来越被理解。
作者于 2020 年 8 月在 PubMed 和会议摘要中搜索了临床前和临床研究，以提供 ET 和 PV 中免疫病理生物学的概述，以及几种新型药物的基本原理。讨论了干扰素和芦可替尼在 ET 和 PV 患者中的最新临床试验，然后概述了该领域的未来挑战，特别是对新型治疗方法的挑战，以及对治疗选择的个体化、分子驱动方法的挑战。目前正在积极评估几种新型药物，并在此进行了综述。
虽然羟基脲仍然是大多数高危 ET 和 PV 患者细胞减少的一线治疗方法，但 IFN 的疾病修饰潜力很有前景，可能使其成为某些患者的首选。分子检测的进步将使预后和治疗选择更具个体化。
