Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Affiliated Bao'an Hospital of Southern Medical University, Shenzhen, Guangdong, China.
Biol Blood Marrow Transplant. 2018 Jul;24(7):1341-1349. doi: 10.1016/j.bbmt.2018.02.026. Epub 2018 Mar 9.
Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disorders (EBV-PTLDs) are rare but potentially fatal complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by uncontrolled proliferation of EBV-infected lymphocytes. The most common risk factors include T cell depletion of graft, HLA mismatch, severe graft-versus-host disease (GVHD), and EBV seromismatch (recipient-negative/donor-positive), among others. EBV-PTLDs commonly manifest as fever and lymphadenopathy and may rapidly progress to multiorgan failure and even death. Histopathological evidence is indispensable for the diagnosis, and positive findings of EBV-DNA (EBV-DNAemia) and imaging are also very helpful. Active prophylaxis, such as optimization of the donor choice, conditioning regimen, and GVHD prevention, or passive prophylaxis, such as low dose of rituximab, unselected donor lymphocyte infusion (DLI), and EBV-specific cytotoxic T lymphocyte (EBV-CTLs) infusion, can decrease the incidence of EBV-DNAemia. Rituximab- based preemptive treatment can prevent EBV-DNAemia from developing into EBV-PTLDs, particularly benefiting recipients with higher loads of EBV-DNA, although the long-term outcome has not been significantly improved. To date, there is no consensus as to whether and when to initiate prophylactic or preemptive treatment. The current treatment strategies for probable and proven EBV-PTLDs include reduction of immunosuppression (RI), rituximab, adoptive cell therapy (DLI or EBV-CTLs), chemotherapy, radiotherapy, and surgery, among which rituximab plus RI is the mainstay. However, the mortality of EBV-PTLDs remains considerably high, and novel strategies merit exploration.
EB 病毒（EBV）相关的移植后淋巴组织增生性疾病（PTLD）是异基因造血干细胞移植（allo-HSCT）的罕见但潜在致命并发症，其特征为 EBV 感染的淋巴细胞不受控制地增殖。最常见的危险因素包括移植物 T 细胞耗竭、HLA 错配、严重移植物抗宿主病（GVHD）和 EBV 血清学错配（受者阴性/供者阳性）等。PTLD 常见表现为发热和淋巴结病，并可能迅速进展为多器官衰竭，甚至死亡。组织病理学证据对于诊断是不可或缺的，而 EBV-DNA（EBV-DNA 血症）和影像学的阳性发现也非常有帮助。主动预防，如优化供者选择、预处理方案和 GVHD 预防，或被动预防，如低剂量利妥昔单抗、非选择供者淋巴细胞输注（DLI）和 EBV 特异性细胞毒性 T 淋巴细胞（EBV-CTL）输注，可降低 EBV-DNA 血症的发生率。利妥昔单抗为基础的抢先治疗可以预防 EBV-DNA 血症发展为 EBV-PTLD，特别是对 EBV-DNA 载量较高的受者有益，尽管长期结果并未显著改善。迄今为止，对于是否以及何时开始预防或抢先治疗尚无共识。疑似和确诊的 EBV-PTLD 的治疗策略包括减少免疫抑制（RI）、利妥昔单抗、过继细胞治疗（DLI 或 EBV-CTL）、化疗、放疗和手术，其中利妥昔单抗加 RI 是主要治疗方法。然而，PTLD 的死亡率仍然相当高，值得探索新的策略。
