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Introduction: The tumor microenvironment (TME) in post-transplant lymphoproliferative disorders (PTLDs) remains unexplored. Tumor infiltrating lymphocytes (TILs) are prognostic in other lymphomas. We assessed the prognostic impact of TILs in monomorphic B-cell PTLD., Methods: TIL density (CD3+ cells/mm 2 ) was determined by CD3 immunohistochemistry in archived diagnostic biopsies from patients diagnosed with monomorphic B-cell PTLD., Results: Amongst monomorphic PTLDs (N = 107), low TIL-count was associated with inferior 2-year progression-free survival (PFS) (41% versus 86%, P = .003) and 2-year overall survival (OS) (52% versus 93%, P = .003) by Kaplan-Meier analysis. Low TIL-count was significant on Cox univariate regression for inferior PFS (HR 4.5, 95% CI 2.0-9.9, P < .001) and OS (HR 4.6, 95% CI 1.8-11.8, P < .001). Multivariate analysis with clinical variables (age ≥60 years, high LDH, stage III/IV, CNS involvement) and TIL-count showed significance for PFS (HR 3.3, 95% CI 1.3-8.3, P = .010) and a non-significant trend for OS (HR 2.6, 95% CI 0.9-7.3, P = .064). A composite score including TILs and clinical variables (age ≥60 years, high LDH, stage III/IV, CNS involvement) effectively stratified monomorphic PTLD patients by PFS and OS (2-year OS: low-risk 93%, intermediate-risk 61%, high-risk 23%, P < .001)., Conclusions: The TME and TILs are prognostically relevant in monomorphic PTLD. Prognostic models including measures of the TME may improve risk stratification for patients with monomorphic PTLDs., Competing Interests: Declaration of Competing Interest AP has attended advisory boards for Janssen, AstraZenica, Roche, Abbvie, Gilead, an Seattle Genetics. She has received honoraria from Janssen, Gilead, and Abbvie. MJ has acted in advisory and consultancy roles for Kite/Gilead, Novartis, BMS, and Takeda. JK has received honoraria from AbbVie, Bristol Myers Squibb, Amgen, AstraZeneca, Celgene, Gilead Sciences, Janssen, Karyopharm Therapeutics, Merck, Novartis, Roche, and Seattle Genetics; has consultancy or advisory roles with AbbVie, Bristol Myers Squibb, Gilead Sciences, Karyopharm Therapeutics, Merck, Roche/Genentech, and Seattle Genetics; and has received research grants or funding from Janssen and Roche. All other authors did not report any relevant conflict of interest disclosures., (Copyright © 2022. Published by Elsevier Inc.)

Classic Hodgkin lymphoma (CHL) is the rarest post-transplant lymphoproliferative disorder (PTLD) subtype. Few cases of patients with metachronous discordant PTLD episodes including CHL-PTLD have been reported, but the incidence of and risk factors for this phenomenon are unknown. Patients with CHL-PTLD were identified from an institutional PTLD database. Of 13 patients identified with CHL-PTLD six (46%) had antecedent non-CHL-PTLD: three had polymorphic PTLD, two monomorphic PTLD, and one nondestructive PTLD. Patients with prior metachronous non-CHL-PTLD were younger at transplant and had a longer latency time to CHL-PTLD post-transplant. The prevalence of EBV seronegativity at transplant was high in both groups, but prolonged high-level EBV DNAemia only occurred in some with metachronous non-CHL-PTLD. In conclusion, patients with CHL-PTLD have metachronous non-CHL-PTLD diagnoses with discordant histology more commonly than previously recognized. Primary EBV infection with chronically elevated EBV viral loads may represent unique risk factors for CHL-PTLD following an initial non-CHL-PTLD event.

Introduction: Epstein-Barr virus (EBV) associated smooth muscle tumors (EBV-SMT) are a rare complication of solid organ transplantation (SOT). Incidence data related to this EBV-SMT are limited. EBV DNA is universally present in these tumors. How these cells get infected with EBV, whether this is a result of primary EBV infection vs reactivation, and how persistent active EBV infection post-transplant influences EBV-SMT pathogenesis remains unknown., Methods: Among 5006 SOT recipients (474 pediatric, 4532 adult) receiving SOT at our center between Jan 1984 and Dec 2015, three cases of post-transplant EBV-SMT were identified., Results: All cases were pediatric heart transplants who were EBV seronegative prior to transplant, and experienced primary EBV infection with persistently elevated EBV viral loads, despite antiviral therapy. Two are deceased at 3.2 and 0.9 years post-diagnosis, while one remains alive 6.2 years post diagnosis. The overall local incidence of post-transplant EBV-SMT at our institution was 0.7 (95% CI, 0.2-1.7) per 1000 patient years, and 2.6 (95% CI, 0.6-6.7) per 1000 patient years in pediatric heart transplants. A literature review identified 36 pediatric and 51 adult cases of post-transplant EBV-SMT., Conclusions: We hypothesize that pre-transplant EBV seronegativity, followed by primary EBV infection and persistently high EBV viral loads, represents a unique risk factor for post-transplant EBV-SMT. Pediatric heart transplant recipients were found to be disproportionately affected by post-transplant EBV-SMT at our institution., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)