Dhakal P, Bhatt V R
Department of Medicine, Michigan State University, East Lansing, MI, USA.
Department of Internal Medicine, Division of Hematology-Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
Bone Marrow Transplant. 2017 Mar;52(3):352-356. doi: 10.1038/bmt.2016.253. Epub 2016 Oct 24.
Diagnosis and management of hematopoietic cell transplant-associated thrombotic microangiopathy (TA-TMA) are very complex and controversial, given multiple ongoing issues and comorbidities in sick transplant recipients. Complement activation via classic and alternative pathways is emerging as a potential pathogenetic mechanism in the development of TA-TMA. Complement-centric diagnostic strategy using functional and genetic tests may possibly support diagnosis, enhance molecular understanding and direct drug development. Complement blockade using eculizumab has shown some promising rates of hematologic responses, however, survival may still be poor. Early discontinuation of calcineurin inhibitor where feasible, use of eculizumab, aggressive infection prophylaxis, close monitoring and early treatment of potential complications including GvHD and organ failure may improve outcomes. A number of complement inhibitors are in the development and may change treatment paradigm. Future studies are important to better understand TA-TMA as a disease process and may aim to confirm the role of complement activation in TA-TMA, enhance diagnostic strategy, determine therapeutic approaches and strategies to reduce the risk of other complications particularly infection and GvHD.
鉴于造血干细胞移植受者存在多种持续问题和合并症，造血细胞移植相关血栓性微血管病（TA-TMA）的诊断和管理非常复杂且存在争议。通过经典途径和替代途径的补体激活正成为TA-TMA发生发展的一种潜在致病机制。使用功能和基因检测的以补体为中心的诊断策略可能有助于诊断、增强分子理解并指导药物研发。使用依库珠单抗进行补体阻断已显示出一些有前景的血液学反应率，然而，生存率可能仍然较低。在可行的情况下尽早停用钙调神经磷酸酶抑制剂、使用依库珠单抗、积极预防感染、密切监测以及早期治疗包括移植物抗宿主病（GvHD）和器官衰竭在内的潜在并发症可能会改善预后。多种补体抑制剂正在研发中，可能会改变治疗模式。未来的研究对于更好地理解TA-TMA这一疾病过程很重要，可能旨在确认补体激活在TA-TMA中的作用、增强诊断策略、确定治疗方法以及降低其他并发症尤其是感染和GvHD风险的策略。
