We examined the associations of Epstein-Barr virus (EBV) status with characteristics and outcomes of post-transplantation lymphoproliferative disorder (PTLD) by studying 176 adult solid organ transplant recipients diagnosed with PTLD between 1990 and 2013 [58 (33%) EBV-negative; 118 (67%) EBV-positive]. The proportion of EBV-negative cases increased over time from 10% (1990–1995) to 48% (2008–2013) (P<.001). EBV-negative PTLD had distinct characteristics (monomorphic histology, longer latency) though high-risk features (advanced stage, older age, high lactate dehydrogenase, central nervous system involvement) were not more common compared to EBV-positive PTLD. In multivariable analysis, EBV negativity was not significantly associated with worse response to initial therapy (adjusted odds ratio, 0.84; P=.75). The likelihood of achieving a complete remission (CR) was not significantly different for EBV-negative versus EBV-positive PTLD including when therapy was reduction of immunosuppression alone (35% vs 43% respectively, P= .60) or rituximab (43% vs 47%, P=1.0). EBV negativity was also not associated with worse overall survival (adjusted hazard ratio, 0.91; P=.71). Our findings indicate that EBV status is not prognostic or predictive of treatment response in adults with PTLD. The high proportion of EBV-negative disease diagnosed in recent years highlights the need for new strategies for prevention and management of EBV-negative PTLD.

8578 Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation. PTLD is frequently linked with Epstein-Barr virus (EBV) and it was suggested that EBV negativity is associated with a poor prognosis and lack of response to reduction of immunosuppression (RI). We conducted a case-control study to identify the characteristics, outcome and response to therapy of EBVpos and EBVneg PTLD over a 20-year period. Methods: We reviewed data on patients diagnosed with PTLD at U. Penn. between 1982 and 2012. We determined EBV positivity on tumor samples according to WHO criteria. We compared clinical and pathologic characteristics, response to therapy, and survival of EBVpos and EBVneg patients. Results: Of 222 patients diagnosed with PTLD, we verified the EBV status of 169 patients, of whom 35% were EBVneg and 65% were EBVpos. Mean follow-up was 46.7 months. Median time from transplant to PTLD was 23.1 mo. in EBVpos vs. 59.3 mo. in EBVneg (p=0.003) with 42% of EBVpos patients being diagnosed within the first year after transplant vs. 15% in the EBVneg group (p<0.001). EBVneg PTLD was more likely to occur in non-thoracic vs. thoracic transplants (p=0.006). 28% of patients with EBVpos PTLD presented with disease originating from the graft vs. 14% in the EBVneg group (p=0.03). In terms of histology, 36% of EBVpos patients had polymorphic PTLD vs. 7% of EBVneg patients (p<0.001). Of patients who were treated with RI alone (40% of patients in both groups), the overall response rates were 50% and 48% in EBVpos and EBVneg patients respectively (p=NS). Response rates to rituximab were also similar. There was no difference in the mortality risk between groups (HR=1.04; p=0.84). The 5-year survival rates were 47% and 51% in EBVpos and EBVneg PTLD respectively (p=NS). Conclusions: In a large single-center series, EBVneg PTLD was associated with late occurrence after transplant, monomorphic histology and similar outcome in comparison with EBVpos PTLD. Importantly, the response of EBVneg PTLD to RI and rituximab was no different than EBVpos PTLD. These results have implications for the management of solid organ transplant recipients with PTLD.