Post Transplant Lymphoproliferative Disorders (PTLD) After Lung Transplantation: Comparison of Patients with Early Versus Late Disease.
Authors: Wudhikarn Kitsada , Holman Carol J , Blaes Anne H , Dunitz Jordan M , Hertz Marshall I , Peterson Bruce A. 
Published: October 2019

Abstract
Abstract 3947
Poster Board III-883
The incidence and natural history of post-transplant lymphoproliferative disorders (PTLD) vary considerably after different types of organ transplantation. Lung and heart-lung transplants pose a higher risk of PTLD than kidney, pancreas or liver transplantation, most likely due to higher intensity post transplant immunosuppression. While the number of lung transplants is growing, there are only a few studies that detail PTLD in this setting. We studied 33 PTLD patients identified among 639 lung transplant recipients (5.1%) seen at the University of Minnesota between January 1985 and December 2008. The median age at diagnosis was 52 years (20-67 years); 17 cases (51%) were male. The median interval from transplantation to PTLD was 95 months (3-242 months). The great majority (91%) presented with extranodal disease; bone marrow involvement was rare (6%). Eight patients (24%) developed PTLD within one year of transplantation (early group) and predominantly had PTLD involving the allograft or other intra-thoracic organs. These patients often presented with subacute respiratory symptoms and evidence of pulmonary infiltration, raising the question of infection or allograft rejection. Twenty five patients (76%) were diagnosed more than one year after transplantation (late group) with disease mainly affecting gastrointestinal organs. Their presentations predominantly included acute abdominal symptoms and GI bleeding. Patients in both the early and late groups had advanced stage disease and high International Prognostic Index scores at diagnosis. Thirteen percent of the early group and 44% of the late group had a poor performance status (PS > 2) (p=0.107). Median LDH was 1117 U/L in the early group and 1830 U/L in the late group (p=0.204). Monomorphic diffuse large B cell lymphoma was the most common pathological diagnosis (86%) in both early and late groups. Ebstein-Barr encoded RNA (EBER) stain was positive in 20 cases (61%) and was not different between the two groups (p=0.177). For management, 31 of the 33 patients (94%) had their immunosuppression reduced and 30 patients also underwent systemic treatment, including rituximab (31%), chemotherapy (36%) or both (33%). The 3 patients who did not receive systemic treatment had progressive disease and died. Eighty seven percent of the early group and 45% of the late group achieved remission. However, there was no statistical difference in treatment response in the two groups (p=0.137). A total of 25 patients (76%) died; median survival was 9 months (0-107 months). Again, there was no statistically significant difference in survival between early and late PTLD (p=0.230). Major causes of death were infection and PTLD. Univariate analysis using the Cox proportional hazards model revealed that treatment response (p<0.001), good performance status (p<0.001) and presence of CD20 (p=0.006) were significant predictors for survival. We conclude that the incidence of PTLD after lung transplantation is high. Although there are clinical differences between those who present early or late, pathologic subtype, treatment response and survival are similar. Patients developing PTLD after lung or heart-lung transplantation have a poor prognosis, with patients dying most commonly from PTLD or infection.

Disclosures:
No relevant conflicts of interest to declare.