Tremblay Douglas, Kosiorek Heidi E, Dueck Amylou C, Hoffman Ronald
Hematology/Oncology Section, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, United States.
Front Oncol. 2021 Feb 16;10:636675. doi: 10.3389/fonc.2020.636675. eCollection 2020.
Thrombosis is the largest contributor to morbidity and mortality in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Our understanding of the risk factors and pathophysiology of thrombosis in PV and ET patients is developing, including recent insights into the role of aberrant platelet-neutrophil interactions, mutated endothelial cells and the pro-thrombotic inflammatory milieu. To date, few available therapies have demonstrated the ability to reduce the thrombotic burden in patients with these diseases. Although numerous therapeutic agents have been investigated in both PV and ET patients, few studies are designed to assess their impact on thrombotic events. In this review, we first describe the burden of thrombosis in patients with these myeloproliferative neoplasms (MPNs) and briefly explore their pathophysiologic mechanisms. We then critically assess and summarize the evidence behind currently available therapies with attention toward thrombotic endpoints. Finally, we describe a path forward for clinical research in MPNs that involves surrogate endpoint validation, biomarker development, and clinical trial design strategies in order to accurately assess reduction of thrombotic events when evaluating novel therapies.
血栓形成是真性红细胞增多症（PV）和原发性血小板增多症（ET）患者发病和死亡的最大原因。我们对PV和ET患者血栓形成的危险因素及病理生理学的认识正在不断发展，包括最近对异常血小板 - 中性粒细胞相互作用、突变内皮细胞及促血栓形成炎症环境作用的新见解。迄今为止，很少有可用的治疗方法能证明有能力减轻这些疾病患者的血栓负担。尽管在PV和ET患者中已经研究了许多治疗药物，但很少有研究旨在评估它们对血栓事件的影响。在本综述中，我们首先描述这些骨髓增殖性肿瘤（MPN）患者的血栓负担，并简要探讨其病理生理机制。然后，我们严格评估并总结目前可用疗法背后的证据，重点关注血栓形成终点。最后，我们描述了MPN临床研究的前进方向，其中涉及替代终点验证、生物标志物开发和临床试验设计策略，以便在评估新疗法时准确评估血栓事件的减少情况。
