Post-Transplant Lymphoproliferative Disease In Liver Transplant Recipients: A Single Institution Experience

Post-transplant lymphoproliferative disease (PTLD) represents a major complication after solid organ transplantation, associated with high morbidity and mortality. Few, mostly small retrospective case series have reported on the clinical features, treatment and outcome of PTLD after liver transplantation, and the optimal treatment approach remains controversial. At our institution, the management of PTLD was not standardized until 2006, when a dedicated lymphoma team for PTLD treatment was formed and adopted a uniform approach based on histologic phenotype. In this approach, monoclonal diffuse large B-cell lymphoma (DLBCL) occurring post transplant was treated aggressively with immunochemotherapy.

We retrospectively analyzed the clinical data of all adult patients who developed PTLD following liver transplantation at our institution between 1988 and 2010. We also compared the outcomes of patients with the most common PTLD histology - DLBCL - treated before 2006 (era 1) and thereafter (era 2).

We identified 26 patients (m=18, f=8) with median age of 60 (range 15–80). Underlying liver diseases included hepatitis C (n=9), non-alcoholic steatohepatitis (n=3), alcoholic cirrhosis (n=3), biliary atresia (n=3), autoimmune hepatitis (n=3), cryptogenic cirrhosis (n=2), hepatitis B (n=1), fulminant hepatic failure (n=1) and congenital syndrome (n=1). Acute transplant rejection that required additional immunosuppressive therapy was observed in 16 (62%). Median latency of PTLD after liver transplantation was 39 (range 1–192) months. Eight patients (31%) presented with early PTLD, i.e. within one year after transplantation. Histologic entities included DLBCL (n=16), polymorphic lymphoplasmacytic infiltrate (n=4), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), Hodgkin lymphoma (n=1) and plasmacytoma (n=1). Tissue staining for EBER was positive in 4/21 evaluated cases (19%). The majority of patients (65%) presented with stage IV disease, and all but one (96%) manifested with extranodal disease. Median IPI score was 3. Initial treatment approaches in patients diagnosed and treated in era 1 (n=13) included reduction or discontinuation of immunosuppression alone (n=2) or in combination with antiviral agents (n=2) and Rituximab (n=7). Two patients died before initiation of therapy. Complete remission to first-line therapy was observed in 3 and partial remission in 4 patients evaluated for response. Six patients in this group died from progressive disease (n=1), infectious complications (n=3), hemorrhagic stroke (n=1) and unknown cause (n=1). Among patients diagnosed and treated in era 2 (n=13), eleven received chemotherapy with or without Rituximab without reduction of immunosppression, one patient was on “watch and wait” for asymptomatic splenic marginal zone lymphoma and another patient decided to seek treatment elsewhere and was lost to follow-up. Eleven patients in this group (1 patient with plasmacytoma of the liver and 10 with DLBCL, including 1 case of primary CNS lymphoma) were evaluable for response and all achieved a complete remission. After a median follow-up period of 28.5 months for surviving patients, the 3-year overall survival (OS) and progression-free survival (PFS) for all patients were 73% and 71%, respectively. One- and 3-year OS was 60% and 51%, respectively, for patients treated in era 1 and 100% for patients treated in era 2 (p=0.01), with 1- and 3-year PFS of 51% in era 1 and 91% in era 2, respectively (p=0.03). Patients with DLBCL histology treated in era 1 had 1- and 3-year OS of 40% and 20% (median 11 months), respectively, while those treated in era 2 had 1- and 3-year OS of 100% (p=0.001), with corresponding 1 and 3-year PFS of 20% (median 8 months) and 90%, respectively (p=0.004).

Our study is one of the largest ever published on PTLD in adult liver transplant recipients. The majority of these patients present with aggressive histologies and high risk features. An aggressive immunochemotherapeutic approach by experienced and dedicated lymphoma and liver transplant teams may benefit post-transplant patients with DLBCL and lead to outcomes similar to those observed in the non-transplant setting.

No relevant conflicts of interest to declare.