Post-Transplantation Lymphoproliferative Disorder in Kidney Transplantation: A Japanese Single-Center Experience

Abstract

Post-transplantation lymphoproliferative disorder (PTLD) is one of the most important complications in transplantation. We experienced 7 cases of PTLD after kidney transplantation and simultaneous pancreas and kidney transplantation from 2004 to 2008. All 7 cases were diagnosed diffuse large B cell lymphoma in pathologically. Our treatment protocol against PTLD is the following. First of all, calcineurin inhibitor (CNI) is discontinued while MMF is only reduced to save graft function from rejection. 375mg/m2 of Rituximab is administrated weekly for 8 consecutive weeks. After 4 weeks of administration of Rituximab, CT should be performed to evaluate effectiveness of the treatment. When CT reveals complete or partial response, administration of Rituximab continues for 4 more weeks, while CHOP is added to Rituximab in case of stable or progressive disease with CT. All 7 cases had a complete remission of PTLD with this protocol. For acquisition of complete remission one case required only reduction of imuunosuppression and two cases required CHOP with Ritaximab. However one□patient among them died with EBV associated leiomyosarcoma after remission of PTLD. 6 cases out of 7 were negative for EBV-VCA IgG and EBV-EBNA IgG (EBV- recipient) before transplantation. EBV- recipients have higher risk than recipients who are positive for EBV-VCA IgG and EBV-EBNA IgG (EBV+ recipient) because only one EBV+ recipient developed PTLD. Therefore, we have been trying to reduce the incidence of PTLD in kidney transplantation especially against EBV- recipients with the following algorithm in our facility since 2009. EBV DNA in blood is quantified by real time PCR monthly in every EBV- recipient. In case of detecting EBV DNA in blood, target trough of tacrolimus is reduced (3-5ng/ml) and reduction of MMF. After induction of this algorithm, only one EBV- recipient developed PTLD. This recipient had a complete remission after receiving reduction of imuunosuppression and administration of Ritaximab. The incidence of PTLD reduced from 4.5% to 0.7% using this algorithm. There were no significant differences in these EBV- recipient between before and after 2009 in EBV DNA does in blood and does of MMF and tacrolimus, however tacrolimus level in before 2009 group was significantly higher than in after 2009 group. These results suggest CNI trough level control is most important to prevent development PTLD in EBV- recipient.