Meijer Ellen, Cornelissen Jan J
Department of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Curr Opin Hematol. 2008 Nov;15(6):576-85. doi: 10.1097/MOH.0b013e328311f438.
Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is a rare but serious complication in recipients of allogeneic stem cell transplants. An overview is given of the incidence, monitoring and (early) treatment of EBV-LPD.
The most important risk factor for EBV-LPD is the use of in-vivo T-cell depletion with antithymocyteglobulin. In addition, alternative donor stem cell transplantation is associated with an increased risk for EBV-LPD. Monitoring of EBV DNA in high-risk patients and subsequent early treatment is very successful, resulting in a low EBV-associated mortality. The monitoring of EBV-specific cytotoxic T lymphocytes might further increase the positive predictive value of EBV DNAemia for EBV-LPD. Once overt EBV-LPD has been diagnosed, rituximab treatment is indicated, guided by monitoring of EBV DNA. The infusion of donor lymphocytes is highly effective, but may be complicated by graft-versus-host disease. Therefore, the infusion of T cells, which have been depleted of alloreactive cells, is currently receiving attention.
EBV DNA levels should be monitored in patients with high-risk features. Early treatment may be instituted at predefined DNA levels (preemptive approach) or at the earliest signs of LPD (prompt approach). Stepwise treatment guided by EBV DNA, including interruption of immunosuppression, rituximab, and adoptive T-cell immunotherapy may all add to the low mortality currently associated with LPD following allogeneic stem cell transplantation.
爱泼斯坦-巴尔病毒相关淋巴增殖性疾病(EBV-LPD)是同种异体干细胞移植受者中一种罕见但严重的并发症。本文对EBV-LPD的发病率、监测及(早期)治疗进行综述。
EBV-LPD最重要的危险因素是使用抗胸腺细胞球蛋白进行体内T细胞清除。此外,替代供者干细胞移植与EBV-LPD风险增加相关。对高危患者监测EBV DNA并随后进行早期治疗非常成功,导致EBV相关死亡率较低。监测EBV特异性细胞毒性T淋巴细胞可能会进一步提高EBV血症对EBV-LPD的阳性预测价值。一旦确诊明显的EBV-LPD,在监测EBV DNA的指导下应使用利妥昔单抗治疗。输注供者淋巴细胞非常有效,但可能并发移植物抗宿主病。因此,目前去除了同种异体反应性细胞的T细胞输注受到关注。
具有高危特征的患者应监测EBV DNA水平。可在预定义的DNA水平(抢先治疗方法)或LPD最早迹象出现时(及时治疗方法)开始早期治疗。以EBV DNA为指导的逐步治疗,包括中断免疫抑制、利妥昔单抗和过继性T细胞免疫治疗,都可能有助于降低目前同种异体干细胞移植后LPD相关的低死亡率。