Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark

Lene Ugilt Pagter Ludvigsen; Anders Åsberg; Signe Spetalen; Mia Dahl Sørensen; Stephen Hamilton-Dutoit; Ann Maria Gramkow; Christian Fynbo Christiansen; Grete Birkeland Kro; Marianne Kragh Thomsen; Sinna Pilgaard Ulrichsen; Rune Micha Pedersen; Harald Holte; Helle Charlotte Thiesson; Anna Bjerre; Francesco D'Amore; Dag Olav Dahle; Bente Jespersen; Søren Jensen-Fangel; Anna Varberg Reisæter

doi:10.1016/j.ajt.2025.01.035

Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark

Lene Ugilt Pagter Ludvigsen^*, Anders Åsberg, Signe Spetalen, Mia Dahl Sørensen, Stephen Hamilton-Dutoit, Ann Maria Gramkow, Christian Fynbo Christiansen, Grete Birkeland Kro, Marianne Kragh Thomsen, Sinna Pilgaard Ulrichsen, Rune Micha Pedersen, Harald Holte, Helle Charlotte Thiesson, Anna Bjerre, Francesco D'Amore, Dag Olav Dahle, Bente Jespersen, Søren Jensen-Fangel, Anna Varberg Reisæter

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

1 Citationer (Scopus)

Abstract

Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.

Originalsprog	Engelsk
Tidsskrift	American Journal of Transplantation
ISSN	1600-6135
DOI	https://doi.org/10.1016/j.ajt.2025.01.035
Status	E-pub / Early view - 2025

Adgang til dokumentet

10.1016/j.ajt.2025.01.035

Andre filer og links

Link to publication in Scopus

Citationsformater

Ludvigsen, L. U. P., Åsberg, A., Spetalen, S., Sørensen, M. D., Hamilton-Dutoit, S., Gramkow, A. M., Christiansen, C. F., Kro, G. B., Thomsen, M. K., Ulrichsen, S. P., Pedersen, R. M., Holte, H., Thiesson, H. C., Bjerre, A., D'Amore, F., Dahle, D. O., Jespersen, B., Jensen-Fangel, S., & Reisæter, A. V. (2025). Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark. American Journal of Transplantation. Advance online publication. https://doi.org/10.1016/j.ajt.2025.01.035

@article{7a0d4a9d030d449c87f8406435e26025,

title = "Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark",

abstract = "Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.",

keywords = "antithymocyte globulin, antiviral prophylaxis, ATG, combined kidney and pancreas transplantation, EBV, Epstein-Barr virus, kidney transplantation, posttransplant lymphoproliferative disease, posttransplant lymphoproliferative disorder, PTLD, rituximab",

author = "Ludvigsen, {Lene Ugilt Pagter} and Anders {\AA}sberg and Signe Spetalen and S{\o}rensen, {Mia Dahl} and Stephen Hamilton-Dutoit and Gramkow, {Ann Maria} and Christiansen, {Christian Fynbo} and Kro, {Grete Birkeland} and Thomsen, {Marianne Kragh} and Ulrichsen, {Sinna Pilgaard} and Pedersen, {Rune Micha} and Harald Holte and Thiesson, {Helle Charlotte} and Anna Bjerre and Francesco D'Amore and Dahle, {Dag Olav} and Bente Jespersen and S{\o}ren Jensen-Fangel and Reis{\ae}ter, {Anna Varberg}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

doi = "10.1016/j.ajt.2025.01.035",

language = "English",

journal = "American Journal of Transplantation",

issn = "1600-6135",

publisher = "Wiley-Blackwell Publishing, Inc.",

}

Ludvigsen, LUP, Åsberg, A, Spetalen, S, Sørensen, MD, Hamilton-Dutoit, S, Gramkow, AM, Christiansen, CF, Kro, GB, Thomsen, MK, Ulrichsen, SP, Pedersen, RM, Holte, H, Thiesson, HC, Bjerre, A, D'Amore, F, Dahle, DO, Jespersen, B , Jensen-Fangel, S & Reisæter, AV 2025, 'Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark', American Journal of Transplantation. https://doi.org/10.1016/j.ajt.2025.01.035

Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark. / Ludvigsen, Lene Ugilt Pagter; Åsberg, Anders; Spetalen, Signe et al.
I: American Journal of Transplantation, 2025.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark

AU - Ludvigsen, Lene Ugilt Pagter

AU - Åsberg, Anders

AU - Spetalen, Signe

AU - Sørensen, Mia Dahl

AU - Hamilton-Dutoit, Stephen

AU - Gramkow, Ann Maria

AU - Christiansen, Christian Fynbo

AU - Kro, Grete Birkeland

AU - Thomsen, Marianne Kragh

AU - Ulrichsen, Sinna Pilgaard

AU - Pedersen, Rune Micha

AU - Holte, Harald

AU - Thiesson, Helle Charlotte

AU - Bjerre, Anna

AU - D'Amore, Francesco

AU - Dahle, Dag Olav

AU - Jespersen, Bente

AU - Jensen-Fangel, Søren

AU - Reisæter, Anna Varberg

PY - 2025

Y1 - 2025

N2 - Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.

AB - Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.

KW - antithymocyte globulin

KW - antiviral prophylaxis

KW - ATG

KW - combined kidney and pancreas transplantation

KW - EBV

KW - Epstein-Barr virus

KW - kidney transplantation

KW - posttransplant lymphoproliferative disease

KW - posttransplant lymphoproliferative disorder

KW - PTLD

KW - rituximab

UR - http://www.scopus.com/inward/record.url?scp=85217933151&partnerID=8YFLogxK

U2 - 10.1016/j.ajt.2025.01.035

DO - 10.1016/j.ajt.2025.01.035

M3 - Journal article

C2 - 39884653

AN - SCOPUS:85217933151

SN - 1600-6135

JO - American Journal of Transplantation

JF - American Journal of Transplantation

ER -

Ludvigsen LUP, Åsberg A, Spetalen S, Sørensen MD, Hamilton-Dutoit S, Gramkow AM et al. Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark. American Journal of Transplantation. 2025. Epub 2025. doi: 10.1016/j.ajt.2025.01.035

Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark

Abstract

Adgang til dokumentet

Andre filer og links

Fingeraftryk

Citationsformater