Birkeland S A, Hamilton-Dutoit S
Department of Nephrology, Odense University Hospital, Odense, Denmark.
Transplantation. 2003 Sep 27;76(6):984-8. doi: 10.1097/01.TP.0000085602.22498.CF.
An association between posttransplant lymphoproliferative disorder (PTLD) and cyclosporine A (CsA) and OKT3 has often been postulated on the basis of retrospective studies, although a randomized study with PTLD as the endpoint will probably never be performed. Because focus on PTLD coincided with the use of these drugs, a bias could be suspected.
In a retrospective, nonrandomized study, we reevaluated all lymphoma-like lesions arising in kidney-transplant patients grafted at our center during 1969 to 1998 and observed up to 2002. Case pathology was reviewed, and an association with Epstein-Barr virus (EBV) infection (and latency pattern) was assessed.
We did not find any significant difference in the incidence of PTLDs when comparing the prednisolone/azathioprine, and CsA eras (P=0.89), the periods before or after OKT3 (P=0.61), and those before or after antilymphocyte globulin (ALG) (P=0.22). Occurrence time was shorter in the CsA (P=0.059), OKT3 (P=0.007), and ALG (P=0.007) eras. In the OKT3 era, 182 patients received, and 224 did not receive, OKT3; after the same observation time, there had been eight and five PTLDs, respectively (P=0.34). The use of mycophenolate mofetil (MMF) was associated with a reduction in the number of PTLDs (P=0.01). EBV was detected in 16 of 21 (76%) cases.
We found no evidence to implicate any one drug regime preferentially in the development of PTLDs. The risk of developing PTLD seems to be a result of the whole transplantation process, which includes the antigenicity of the foreign graft, the immunosuppression resulting in inadequate cytotoxic T-cell activity, and the result of EBV infection. An important minority of cases are EBV negative.
尽管可能永远不会进行以移植后淋巴细胞增生性疾病（PTLD）为终点的随机研究，但基于回顾性研究，常假定PTLD与环孢素A（CsA）和OKT3之间存在关联。由于对PTLD的关注与这些药物的使用相吻合，可能会怀疑存在偏差。
在一项回顾性、非随机研究中，我们重新评估了1969年至1998年在我们中心接受肾脏移植且随访至2002年的患者中出现的所有淋巴瘤样病变。回顾病例病理，并评估与爱泼斯坦-巴尔病毒（EBV）感染（及潜伏模式）的关联。
比较泼尼松龙/硫唑嘌呤时代和CsA时代时，我们发现PTLD的发生率无显著差异（P = 0.89）；比较使用OKT3之前或之后的时期，PTLD发生率无显著差异（P = 0.61）；比较使用抗淋巴细胞球蛋白（ALG）之前或之后的时期，PTLD发生率也无显著差异（P = 0.22）。CsA时代（P = 0.059）、OKT3时代（P = 0.007）和ALG时代（P = 0.007）的发病时间较短。在OKT3时代，182例患者接受了OKT3，224例未接受；经过相同观察时间后，分别有8例和5例发生PTLD（P = 0.34）。霉酚酸酯（MMF）的使用与PTLD数量减少相关（P = 0.01）。21例病例中有16例（76%）检测到EBV。
我们没有发现任何证据表明任何一种药物方案在PTLD的发生中具有优先关联。发生PTLD的风险似乎是整个移植过程的结果，这包括异体移植物的抗原性、导致细胞毒性T细胞活性不足的免疫抑制以及EBV感染的结果。一小部分重要病例为EBV阴性。
