University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
Clin Cancer Res. 2011 Sep 15;17(18):5858-66. doi: 10.1158/1078-0432.CCR-11-0804. Epub 2011 Aug 3.
Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are clinically similar disorders characterized by microvascular thrombosis, hemolysis, thrombocytopenia, and end-organ damage. Although they may present with overlapping symptoms, multiple etiologies have been proposed for these thrombotic microangiopathies (TMA). Chemotherapy-induced TMA, which has been described with the use of mitomycin, gemcitabine, and other drugs, has a poor prognosis. Recently, reports of TMA associated with targeted cancer agents have surfaced in the literature. We discuss the clinical presentation, outcome, and etiology of TMA reported with the use of immunotoxins, monoclonal antibodies, and tyrosine kinase inhibitors. A search of PubMed and meeting abstracts was conducted for cases of TMA with the use of targeted cancer agents. The defining symptoms, laboratory values, time to onset, and patient outcomes were compiled. Consistent definitions of TMA and grading of severity in these cases are lacking. However, presentation of TMA in these cases revealed the importance of monitoring for renal toxicity, hemolysis, and thrombocytopenia. Patient outcomes seem to differ from those seen in cases of chemotherapy-induced TMA and may reflect a different underlying etiology. Little is known about the pathogenesis of TMA with targeted cancer agents. In contrast to chemotherapy-induced TMA, partial to full reversibility may be a common outcome. However, further research is warranted into optimal management of patients diagnosed with TMA following treatment with targeted agents.
血栓性血小板减少性紫癜(TTP)和溶血性尿毒症综合征(HUS)是两种临床相似的疾病,其特征为微血管血栓形成、溶血、血小板减少和终末器官损伤。虽然它们可能表现出重叠的症状,但已经提出了多种病因来解释这些血栓性微血管病(TMA)。化疗诱导的 TMA 已在使用丝裂霉素、吉西他滨和其他药物的情况下被描述,其预后较差。最近,文献中出现了与靶向癌症药物相关的 TMA 报告。我们讨论了使用免疫毒素、单克隆抗体和酪氨酸激酶抑制剂时报告的 TMA 的临床表现、结果和病因。我们在 PubMed 和会议摘要中搜索了使用靶向癌症药物的 TMA 病例。汇总了 TMA 的症状、实验室值、发病时间和患者结局。这些病例中 TMA 的定义和严重程度分级并不一致。然而,这些病例中 TMA 的表现揭示了监测肾毒性、溶血和血小板减少的重要性。患者结局似乎与化疗诱导的 TMA 病例不同,这可能反映了不同的潜在病因。对于靶向癌症药物引起的 TMA 的发病机制知之甚少。与化疗诱导的 TMA 相比,部分至完全逆转可能是常见的结局。然而,对于接受靶向药物治疗后诊断为 TMA 的患者的最佳管理,还需要进一步研究。