Post-Transplant Lymphoproliferative Disorder in Lung Transplant Recipients – a Shift Lo Late Onset Disease
Authors: Muchtar Eli , Vidal Liat , Ram Ron , Gurion Ronit , Rosenblat Yivgenia , Bakal Ilana , Kramer Mordechai , Shpilberg Ofer 
Published: October 2019

Abstract
Abstract 5075

Background:
Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication after solid organ transplantation. Most cases of PTLD arise within the first year from transplantation and are associated with EBV infection. However, there are increasing reports on a late onset form of PTLD.

Methods:
We reviewed all charts of patients undergoing either lung or heart-lung transplantation in a tertiary center in Israel between the years 1997 and 2012. PTLD was defined according to the WHO criteria. We analyzed baseline characteristics, clinical and pathological parameters as well as transplantation outcomes.

Results:
We identified 9 PTLD patients among cohort of 336 lung and heart-lung transplant recipients (incidence=2. 7%). Additional PTLD patient from another hospital was added for the clinical analysis (10 patients overall). Median age at transplantation of the PTLD patients was 50 (range 11–63) years, compared to 56 (2–69) among the non-PTLD patients (p=0. 04). Idiopathic pulmonary fibrosis was the leading etiology for transplantation among both PTLD and non-PTLD patients (50% vs. 37. 2%, respectively, p=0. 5), while relatively less COPD patients were observed among PTLD patients (10% vs. 34%, respectively, p=0. 28). Median time from transplantation to PTLD diagnosis was 41 (range 3–128) months, being among the longest to be reported in the literature among lung transplant recipients. Three patients developed early PTLD in our cohort, all were pre-transplant EBV seronegative and all were asymptomatic, diagnosed during surveillance chest imaging. In contrast, the seven late-onset PTLD cases were all EBV seropositive prior to transplantation, and were diagnosed after presenting with various symptoms, mainly B symptoms (71%). Overall extra-nodal involvement at presentation was very common for both PTLD forms (90%). While early onset PTLD uniformly involved the transplanted lung, this was relatively rare in the late-PTLD (100% vs. 14%, p=0. 03). According to the WHO classification, all PTLD specimens were monoclonal, based on molecular or light chain immuno-histochemistry. Eight (80%) cases were CD20 positive B cell lymphomas. EBV staining in the specimens was positive in 7 patients, including the 3 early-onset PTLD cases.
All patients were treated with reduction of immunosuppression (Table). Other treatment modalities were diverse, including combination chemotherapy (6 patients), rituximab (6 patients), surgery (1 patient) and antiviral treatment (2 patients). 8 (80%) patients attained complete remission. With a median follow-up of 23 months, 6 patients died (3 from chronic rejection of the transplant, 1 from late chemotherapy toxicity, 1 from disease progression and 1 from unrelated cause). The median time from PTLD diagnosis to death was 19 months. Of the 8 patients attaining complete remission, only three patients are alive at the end of follow-up.

Conclusion:
Our cohort of lung transplant recipients demonstrates a trend of late-onset PTLD. This might be related to the high pre-transplant sero-prevalence to EBV in our cohort (96. 3%), as late-onset PTLD has been reported to be less associated with EBV proliferation. The majority of PTLD patients in our cohort died of treatment-related causes rather than disease progression.

Disclosures:
No relevant conflicts of interest to declare.