Introduction: PTLD remain a feared complication of organ and tissue transplant, with high morbidity and mortality. While 50-80% of cases are strongly associated with Epstein-Barr virus (EBV), neither the presence of EBV in the tissue nor most other clinical/epidemiological/tumor characteristics are consistently associated with worse allograft or patient survival.

Methods: Through advances in nucleic acid sequencing, we were able to extract, enrich and detect nucleic acids of multiple viruses simultaneously from stored paraffin-embedded tissues of PTLD at our center, then correlate the sequencing data to available clinical data on tumor characteristics and outcomes in our electronic medical record.

Results: Our study population comprised PTLD tissues from 61 subjects between 1994-2015 and 8 positive and 6 negative control tissues. The demographics of the PTLD cases were: mean age 24.6 years at transplant, 55% under 18 years age at transplant, 61% male, 54% B cell lineage, 63% monomorphic type, 44% presented beyond 1-year post-transplant, transplant organ lung 39%, kidney 26%, heart 15%. We found EBV sequences in 63%. In the tissues that were EBV negative by sequencing, no other viral sequences were more prevalent. Roseolovirus sequences were more prevalent in EBV positive tissues. Discrepancies of negative sequencing data and positive immunostaining/in situ hybridization for tissue EBV were present in 9 cases, explainable in most by low percentage focal scattered staining characteristics. Polymorphic type, disseminated location and history of bone marrow transplant were significantly associated with worse allograft survival after PTLD. While tumor WHO classification, clonality and EBV positivity by either sequencing or staining did not associate with patient survival, disseminated location and anellovirus sequence detection in the tumor was significantly associated with worse patient survival (38% alive of anellovirus positive cases versus 68% of negative, p = 0.02). No demographic, transplant or immunosuppression covariates associated with patient or allograft survival.

Conclusions: The presence of anellovirus nucleic acid sequences in PTLD tissue, considered to be an over-immunosuppression marker by others, was associated with worse patient survival in our PTLD series. Further confirmation in larger multicenter studies is desirable.

CITATION INFORMATION: Dharnidharka V, Chen R, Ruzinova M, Parameswaran P, O'Gorman H, Wylie K, Storch G. Presence of Anellovirus Nucleic Acid Sequences in Involved Tissue Is Associated with Worse Patient Survival in Post-Transplant Lymphoproliferative Disorder. Am J Transplant. 2017;17 (suppl 3).

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