The Outcome of Lymphoproliferative Disorder in Liver Transplant Recipients May Correlate with Age at Diagnosis and the Use of Chemotherapy: A Single Centre Report.
Authors: Bagot Catherine N. , Kulasekararaj Austin , Ramalingam Sandeep , Heaton Nigel , O’Grady John , Hadzic Dino , Portmann Bernard , Rela Mohamed , Salisbury Jon , Devereux Steven , Mufti Ghulam J. , Pagliuca Antonio 
Published: April 2020

Abstract
Post transplant lymphoproliferative disorder (PTLD) occurs with an incidence of 1.7–3.3% and 5.6–13% in adults and children respectively. Mortality remains high with rates of 40–70%; approximately double that of other high grade lymphoproliferative disorders. To date, no preventative or therapeutic regimen has been shown to have an overall survival advantage. We examined the clinical and histological features of 31 adults and children diagnosed with PTLD following liver transplantation in a single centre to determine which factors might influence clinical outcome. Patient records were reviewed from the database of cases at King’s College Hospital from 1988–2005 including both children and adults. 60 cases were identified and in 31 cases, relevant data could be obtained. This gave an incidence of PTLD of 1.7% and 2.7% in adults and children respectively. 10 of the 31 cases were children. Most children had an original diagnosis of extra hepatic biliary atresia; the adults had a broad range of primary liver disease. At the time of diagnosis of PTLD, the mean age was 34 years (1.5–64). The mean onset of PTLD from the time of liver transplantation was 50 months (3–156). Approximately equal numbers of patients were on either 1, 2 or 3 forms of immunosuppression when diagnosed. 12 patients presented with extranodal disease and 13 with Stage 4 disease. In 18 patients the IPI could be assessed, with 14 having an IPI of 2 or more. The histological diagnosis in 20 patients was high grade B cell lymphoma, 1 high grade T cell, 1 TNK cell, 1 Hodgkins, 1 low grade B cell, 1 mixed cell, 1 B cell, 1 high grade, 1 plasmacytoid variant and in 3 cases the histological diagnosis was unknown. The tissue affected by lymphoproliferative disease was positive for EBV in 22 cases and 6 patients (all aged &lt;15) were positive for EBV DNA in the serum at diagnosis. Only one adult was tested and found to be negative. All patients were treated with immunoreduction with 18 receiving chemotherapy. 14 patients also received antivirals. 6 patients were treated with immunoreduction alone. Cytotoxic T lymphocytes were used in 2 cases. Chemotherapy used included CHOP, CHOPR and Rituximab alone. 16 patients had a complete response, 2 a partial response and 9 no response. In 4 patients the outcome was unknown. The median follow up was 12.5 months (1–166). Overall survival was 40.36% with median survival at 1 year being 59%. Using univariate analysis, favourable outcome was associated with age &lt;15 at diagnosis (p=0.04) and treatment with chemotherapy (p&lt;0.01). Overall survival in those patients developing PTLD&gt;1 year post transplant was 52.6% compared to 25% in those developing PTLD&lt;1 year post transplant (p=0.28). 1 patient treated with immunoreduction alone survived. Longer term remissions appear to be achieved in younger patients, those who present later following liver transplantation and in whom chemotherapy is used. The amount of immunosuppression, EBV positivity of tissue and stage of disease at presentation do not appear to influence outcome. IPI scores are high in many patients although it remains unclear whether these are applicable to PTLD.