Analysis of Post-Transplant Lymphoproliferative Disorder (PTLD) Outcomes with Epstein–Barr Virus (EBV) Assessments—A Single Tertiary Referral Center Experience and Review of Literature

Abstract

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations ranging from polyclonal reactive proliferations to overt lymphomas that develop as consequence of immunosuppression in recipients of solid organ transplantation (SOT) or allogeneic bone marrow/hematopoietic stem cell transplantation. Immunosuppression and Epstein–Barr virus (EBV) infection are known risk factors for PTLD. Patients with documented histopathologic diagnosis of primary PTLD at our institution between January 2000 and October 2019 were studied. Sixty-six patients with PTLD following SOT were followed for a median of 9.0 years. The overall median time from transplant to PTLD diagnosis was 5.5 years, with infant transplants showing the longest time to diagnosis at 12.0 years, compared to pediatric and adolescent transplants at 4.0 years and adult transplants at 4.5 years. The median overall survival (OS) was 19.0 years. In the monomorphic diffuse large B-cell (M-DLBCL-PTLD) subtype, median OS was 10.7 years, while median OS for polymorphic subtype was not yet reached. There was no significant difference in OS in patients with M-DLBCL-PTLD stratified by quantitative EBV viral load over and under 100,000 copies/mL at time of diagnosis, although there was a trend towards worse prognosis in those with higher copies.

Multicenter study of pediatric Epstein‐Barr virus–negative monomorphic post solid organ transplant lymphoproliferative disorders

“…EBV viral load has been reported to have poorer survival in a study of combined adult and pediatric PTLD but the 22% of patients with EBV(−) tumors were not analyzed separately. 35 Frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangements, were reported in 31% and gain or amplification in 50% of nonrearranged cases. 36 Interestingly, three of 19 (15.8%) patients in our study with available MYC FISH had tumors with MYC gene rearrangements, and one had MYC copy number gain.…”

Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder

“…Historically, higher mortality rates were reported in post-alloHSCT PTLD [ 43 ], compared to post-SOT PTLD [ 30 , 35 , 44 ]. However, most recently, this paradigm has shifted and outcomes have overall improved with the introduction of rituximab into clinical practice [ 45 , 46 , 47 ]. Notably, in PTLD where reduction in IST is not feasible, commonly in cases of cardiac transplant, prognosis remains poor [ 46 , 48 ].…”

Nonhepatic Cancer in the Pediatric Liver Transplant Population: Guidelines From the ILTS-SETH Consensus Conference

“…26,37,40,42 Reduction or cessation of immunosuppression remains the first-line treatment in the algorithmic management of EBV/PTLD. 30,37,40,42,43 This strategy is based on the hypothesis that recovery of the host's immune system allows the cytotoxic T lymphocytes to act against EBV and consequently control EBV-driven B-cell proliferation. Success of this treatment strategy is usually clinically evident within 2-4 wk of initiating immunosuppression reduction.…”

“…Monitoring EBV DNA levels may be of value in higher-risk recipients, with frequencies ranging weekly in the first 6 mo after LT to monthly thereafter for at least the first year. 36,37 A definitive diagnosis of PTLDs is made by tissue histopathology, which should further be tested for EBV and CD20 status. 30,[34][35][36] PTLD cases should be classified using the World Health Organization 2017 classification system for tumors of hematopoietic and lymphoid tissues.…”