Creighton University Medical Center, Department of Medicine, Omaha, NE, USA.
Drugs. 2012 Aug 20;72(12):1631-43. doi: 10.2165/11635690-000000000-00000.
Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of potentially life-threatening complications that occur after solid organ and bone marrow transplantation. Risk factors for acquiring PTLD are type of organ transplanted, age, intensity of immunosuppression, viral infections such as Epstein-Barr virus (EBV) and time after transplantation. Due to a dearth of well designed prospective trials, treatment for PTLD is often empirical, with reduction in immunosuppression accepted as the first step. Rituximab, a monoclonal antibody directed against the CD20 antigen of immature B cells, is often used as monotherapy after reduction in immunosuppression, although this is associated with a high risk of relapse if patients have at least one of the following risk factors: age greater than 60 years, elevated lactate dehydrogenase levels and Eastern Cooperative Oncology Group Score between 2 and 4. For such patients, rituximab should be considered in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), particularly if high-grade PTLD is present. Although widely prescribed, the use of ganciclovir for PTLD remains controversial as EBV-transformed cells lack the thymidine kinase necessary for ganciclovir activation. Newer antivirals that combine ganciclovir with activators of cellular thymidine kinase have shown promising results in preclinical studies. In the absence of controlled trials, surgery may be indicated for localized disease and radiotherapy for patients with impending spinal cord compression or disease localized to the central nervous system or orbit. Future interventions may include adoptive immunotherapy, intravenous immunoglobulin, mammalian target of rapamycin inhibitors, monoclonal antibodies to interleukin-6 and galectin-1, and even EBV vaccination. Although several trials are in progress, it is necessary to wait for the long-term outcome of these studies on risk of PTLD relapse.
移植后淋巴组织增生性疾病（PTLD）是一组潜在威胁生命的并发症，发生在实体器官和骨髓移植后。获得 PTLD 的危险因素包括移植器官的类型、年龄、免疫抑制的强度、病毒感染（如 EBV）和移植后的时间。由于缺乏精心设计的前瞻性试验，PTLD 的治疗通常是经验性的，减少免疫抑制被认为是第一步。利妥昔单抗是一种针对幼稚 B 细胞 CD20 抗原的单克隆抗体，在减少免疫抑制后常被用作单一疗法，尽管如果患者有以下至少一个危险因素，复发风险很高：年龄大于 60 岁、乳酸脱氢酶水平升高和东部合作肿瘤组评分在 2 到 4 之间。对于这些患者，应考虑将利妥昔单抗与 CHOP（环磷酰胺、多柔比星、长春新碱和泼尼松）联合使用，特别是如果存在高级别 PTLD。尽管广泛应用，但更昔洛韦用于 PTLD 的使用仍存在争议，因为 EBV 转化的细胞缺乏用于更昔洛韦激活的胸苷激酶。在临床前研究中，将更昔洛韦与细胞胸苷激酶激活剂结合使用的新型抗病毒药物显示出有希望的结果。在没有对照试验的情况下，手术可能适用于局部疾病，放疗适用于即将发生脊髓压迫或疾病局限于中枢神经系统或眼眶的患者。未来的干预措施可能包括过继免疫疗法、静脉注射免疫球蛋白、哺乳动物雷帕霉素靶蛋白抑制剂、白细胞介素-6 和半乳糖凝集素-1 的单克隆抗体，甚至 EBV 疫苗接种。虽然正在进行几项试验，但有必要等待这些研究对 PTLD 复发风险的长期结果。
