Transcriptomic Signatures of EBV-Positive vs. EBV-Negative Post-Transplant Lymphoproliferative Disorder: A Systematic Literature Review

Post-transplant lymphoproliferative disorder (PTLD) represents a heterogeneous spectrum of lymphoid proliferations arising in transplant recipients due to iatrogenic immunosuppression. While Epstein-Barr virus (EBV) drives the majority of cases through viral oncoproteins, 20-40% of PTLD cases are EBV-negative and represent a distinct biological entity with different pathogenic mechanisms. This systematic literature review synthesizes current knowledge regarding PTLD epidemiology, classification, and treatment; EBV biology and oncogenic mechanisms; transplant immunology; and transcriptomic methodologies applied to lymphoproliferative disorders. Critical molecular distinctions between EBV-positive and EBV-negative PTLD are examined, including differential gene expression patterns, genomic alterations, and clinical implications. The review identifies knowledge gaps that support development of transcriptomic signatures and biomarkers for improved diagnosis, prognosis, and therapeutic targeting in PTLD. Index Terms—Post-transplant lymphoproliferative disorder, Epstein-Barr virus, transcriptomics, gene expression profiling, biomarkers, transplant oncology