Incidence and outcome of post-transplant lymphoproliferative disorders in lung transplant patients: Analysis of ISHLT Registry

Zaffiri, Lorenzo; Long, Alex B.; Neely, Megan L.; Cherikh, Wida S.; Chambers, Daniel C.; Snyder, Laurie D.

doi:10.1016/j.healun.2020.06.010

Cited by 17 publications

(14 citation statements)

References 31 publications

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“…However, the optimal way to interpret and monitor EBV DNAemia is not currently established. Moreover, the cumulative incidence of PTLD is estimated around 2% during the 1st year after LT 40 . Thus, there are challenges in generating larger sample size.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of host cellular responses to Epstein–Barr virus (EBV) in adult lung transplant patients with EBV‐associated diseases

Zaffiri

Messinger

Bush

et al. 2023

Journal of Medical Virology

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Epstein-Barr virus (EBV) reactivation is commonly observed in lung transplant recipients (LTRs). However, cellular immune responses to EBV in adult LTRs have not been well described. We aimed to study CD4/CD8 ratio, EBV-specific T cells polyfunctional responses and phenotypic changes in natural killer (NK) cells in adult LTRs presenting with EBV-associated diseases. The CD4/CD8 ratio was significantly decreased in LTRs with EBV DNAemia compared with LTRs without EBV DNAemia and healthy controls (HCs). Stimulation with EBV lytic antigen BZLF1 peptide pools induced significant individual and polyfunctional responses from CD8 + CD69 + T cells.Frequencies of CD8 + CD69 + T cells expressing CD107a were significantly higher in LTRs without EBV DNAemia than in LTRs with DNAemia. Frequencies of CD8 + CD69 + T cells concurrently expressing CD107a, IFN-γ, and TNF-α were significantly greater in LTRs with and without EBV DNAemia than in HCs. Finally, BZLF1 induced significantly higher frequencies of CD8 + CD69 + T cells expressing CD107a and IFN-γ in LTRs without EBV DNAemia when compared with EBNA3B.Frequency of more differentiated CD56 dim CD16 pos NK cells was significantly decreased in LTRs with EBV DNAemia and PTLD compared with HCs. In conclusion, we noted the presence of significant changes in circulating cellular immune responses to EBV in adult LTRs.

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Section: Discussionmentioning

confidence: 99%

Evaluation of host cellular responses to Epstein–Barr virus (EBV) in adult lung transplant patients with EBV‐associated diseases

Zaffiri

Messinger

Bush

et al. 2023

Journal of Medical Virology

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“…However, they are often hampered by their heterogenous population and limited numbers of patients. Large reports from national registries often contain many more cases, but lack detailed information ( 3 , 15 ). Furthermore, significant progress has been made in the past 30 years including a new WHO 2017 classification and improvement of treatment by the introduction of monoclonal antibodies against CD20.…”

Section: Introductionmentioning

confidence: 99%

Characteristics and Outcome of Post-Transplant Lymphoproliferative Disorders After Solid Organ Transplantation: A Single Center Experience of 196 Patients Over 30 Years

Vergote¹,

Deroose²,

Fieuws

et al. 2022

Transpl Int

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Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication after transplantation. In this retrospective, monocentric study we aimed to collect real life data regarding PTLD and determine the role of Epstein Barr Virus (EBV) status and year of diagnosis on prognosis. We identified 196 biopsy-proven PTLD after solid organ transplantation (SOT) diagnosed at the University Hospitals Leuven (Belgium) from 1989 to 2019. EBV status was positive in 61% of PTLD. The median overall survival (OS) was 5.7 years (95% CI: 2.99–11.1). Although EBV positivity was not significantly correlated with OS in multivariate analyses (HR: 1.44 (95% CI: 0.93–2.24); p = 0.10), subgroup analysis showed a significantly better median OS for EBV negative post-transplant diffuse large B-cell lymphoma (DLBCL) compared to EBV positive post-transplant DLBCL (8.8 versus 2.5 years respectively; p = 0.0365). There was a significant relation between year of PTLD diagnosis and OS: the more recent the PTLD diagnosis, the lower the risk for death (adjusted HR: 0.962 (95% CI: 0.931–0.933); p = 0.017). In conclusion, the prognosis of PTLD after SOT has improved in the past decades. Our analysis shows a significant relation between EBV status and OS in post-transplant DLBCL.

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“…1 About 80% of all PTLD cases after solid organ transplantation show the presence of Epstein-Barr virus (EBV) in the tumor tissue. 2 PTLD is associated with up to 50% mortality rate in adult lung transplant recipients, 3 which is higher than other organ transplantations and is likely due to stronger immunosuppression regimens.…”

Section: Introductionmentioning

confidence: 99%

“…12 Moreover, the link between the timing of PTLD onset in lung transplant recipients, such as early-onset PTLD (within first 12 months posttransplantation) versus late-onset PTLD (after 12 months posttransplantation) and survival remains inadequately explored. 1,3 Likewise, little is known whether the heterogeneous EBV latency program expression is related to the development of PTLD in the setting of immunosuppression. Should there be an association between the timing of PTLD onset and the type of EBV latency program, such findings could have clinical significance in measuring risks of PTLS and/or the creation of individualized therapies.…”

Section: Introductionmentioning

confidence: 99%

“…Although initial reports suggested worse outcomes in EBV‐negative PTLD, 10,11 more recent studies have not supported this finding 12 . Moreover, the link between the timing of PTLD onset in lung transplant recipients, such as early‐onset PTLD (within first 12 months posttransplantation) versus late‐onset PTLD (after 12 months posttransplantation) and survival remains inadequately explored 1,3 . Likewise, little is known whether the heterogeneous EBV latency program expression is related to the development of PTLD in the setting of immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

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Evidence of Epstein‐Barr virus heterogeneous gene expression in adult lung transplant recipients with posttransplant lymphoproliferative disorder

Zaffiri

Frankel

Bush

et al. 2021

Journal of Medical Virology

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Epstein‐Barr virus (EBV)‐driven posttransplant lymphoproliferative disorder (PTLD) is a serious complication following lung transplant. The extent to which the presence of EBV in PTLD tissue is associated with survival is uncertain. Moreover, whether the heterogeneity in expression of EBV latency programs is related to the timing of PTLD onset remains unexplored. We retrospectively performed a comprehensive histological evaluation of EBV markers at the tissue level in 34 adult lung transplant recipients with early‐ and late‐onset PTLD. Early‐onset PTLD, occurring within the first 12 months posttransplant, had higher odds to express EBV markers. The presence of EBV in PTLD was not associated with a difference in survival relative to EBV‐negative tumors. However, we found evidence of heterogeneous expression of EBV latency programs, including type III, IIb, IIa, and 0/I. Our study suggests that the heterogeneous expression of EBV latency programs may represent a mechanism for immune evasion in patients with PLTD after lung transplants. The recognition of multiple EBV latency programs can be used in personalized medicine in patients who are nonresponsive to traditional types of chemotherapy and can be potentially evaluated in other types of solid organ transplants.

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Incidence and outcome of post-transplant lymphoproliferative disorders in lung transplant patients: Analysis of ISHLT Registry

Abstract: All rights reserved. No reuse allowed without permission.

Cited by 17 publications

References 31 publications

Evaluation of host cellular responses to Epstein–Barr virus (EBV) in adult lung transplant patients with EBV‐associated diseases

Evaluation of host cellular responses to Epstein–Barr virus (EBV) in adult lung transplant patients with EBV‐associated diseases

Characteristics and Outcome of Post-Transplant Lymphoproliferative Disorders After Solid Organ Transplantation: A Single Center Experience of 196 Patients Over 30 Years

Evidence of Epstein‐Barr virus heterogeneous gene expression in adult lung transplant recipients with posttransplant lymphoproliferative disorder

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