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Posttransplant Lymphoproliferative Disorder in Liver Transplanted Patients – Experience of University Hospital Merkur

Background: Post transplant lymphoproliferative disorder (PTLD)is an increasingly recognised condition as the number of solid organ and bone-marrow transplant recipients increases. It can be a life threatening fulminant disorder and affects approximately 8% of solid organ transplant recipients. EBV replication is successfully controlled in immunocompetent hosts by cytotoxic CD8+ T-cells. The majority of cases of PTLD arise in response to primary infection with EBV or to re-activation of previously acquired EBV. Impaired T-cell immunity in the posttransplantation period can lead to the development of EBV-associated PTLD. The principal risk factors underlying the development of a PTLD are the degree of overall immunosuppression and the EBV serostatus of the recipient. An accurate diagnosis requires a high index of suspicion, since the disorder may present subtly and/or extranodally. The management of PTLD poses a major therapeutic challenge and although there is reasonable agreement about the overall principles of treatment, there is still considerable controversy about the optimal treatment of individual patients. EBV-related PTLD is a significant cause of mortality in patients undergoing OLT with high observed mortality rate (up to 50%). This paper represents the experience of Merkur University Hospital in the diagnosis and treatment of patients with liver transplantation and PTLD. Aim: The aim of this study was to estimate the frequency of EBVrelated PTLD in a cohort of patients undergoing orthotropic liver transplantation (OLT) and to describe clinical, virological and immunological features in these patients. Methods: A cohort of 560 patients undergoing OLT was monitored between 2001 and 2012 at the Merkur University Hospital, Zagreb to identify patients with EBV-related PTLD. Relevant clinical and diagnostic parameters were monitored before transplantation and during the post-transplantation follow-up. All patients were serologically tested for infections with EBV, cytomegalovirus (CMV). EBV- and CMV-viremia were analyzed before transplantation and every 4 weeks after transplantation by PCR. Results: Based on the clinical and diagnostic monitoring of a cohort of transplanted patients, presumptive diagnosis of EBV-related LPDwas established in six of 560 patients (1%). All patients were men. Five patients were diagnosed with PTLD and one patient developed Hodgkin’s lymphoma. PTLD patients were diagnosed with CD20- positive B-cell non-Hodgkin’s lymphoma between 2 and 54 months after transplantation. PTLD morphology was polymorphic in three patients and monomorphic (diffuse large B-cell lymphoma like) in two patients. Four of six patients with EBV-associated LPD died while two patients achieved full remission. Median survival of patients after the diagnosis was 1.6 months. Of four PTLD patients, two died due to the progression of clinical symptoms related to PTLD and two due to other complications. Two PTLD patient that responded to rituximab treatment are alive and in complete remission. All patients were serologically positive for EBV infection before transplantation. Active viral replication in the blood was shown in five of six patients during the post-transplantation period. Conclusion: EBV-related PTLD is significant cause of mortality in patients undergoing OLT. Longitudinal monitoring of EBV-viremia in transplanted

Posttransplant Lymphoproliferative Disorder; Liver Transplantation

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