The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients

Neval E Wareham; Amanda Mocroft; Henrik Sengeløv; Caspar Da Cunha-Bang; Finn Gustafsson; Carsten Heilmann; Martin Iversen; Nikolai S Kirkby; Allan Rasmussen; Søren Schwartz Sørensen; Jens D Lundgren; MATCH in PERSIMUNE study group

doi:10.1007/s00432-018-2674-9

The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients

Neval E Wareham, Amanda Mocroft, Henrik Sengeløv, Caspar Da Cunha-Bang, Finn Gustafsson, Carsten Heilmann, Martin Iversen, Nikolai S Kirkby, Allan Rasmussen, Søren Schwartz Sørensen, Jens D Lundgren, MATCH in PERSIMUNE study group

Department of Clinical Medicine

10 Citations (Scopus)

Abstract

PURPOSE: Emerging EBV DNAemia in plasma is considered an early sign of post-transplant lymphoproliferative disorder (PTLD). The aim of this study was to quantify the extent of benefit from screening for EBV DNAemia to detect emerging PTLD among solid organ (SOT) or hematopoietic stem cell transplant recipients (HSCT).

METHODS: We used receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD. Among 2642 recipients transplanted between January 2004 and December 2014, 79 (3%) developed PTLD.

RESULTS: EBV DNAemia was observed in 331/1784 recipients (18.6%, 95% CI 16.8-20.4) with measured EBV DNA. The area under the curve (AUC) of the ROC of EBV DNAemia to identify persons with subsequent PTLD was 72% (95% CI, 64-79%) among SOT and 59% (51-68%) among HSCT. Including clinical predictors such as age, gender, transplant year and type, high-risk EBV serostatus, and routine biochemistry in addition to EBV DNAemia increased AUC to 83% (75-90%) among SOT and 84% (79-89%) among HSCT. Among HSCT, including additional factors such as T-cell-depleting treatment, acute graft vs. host disease and donor match increased AUC to 85% (78-91%).

CONCLUSIONS: We constructed a model to better predict PTLD compared to EBV DNA screening alone which could have clinical implications.

Original language	English
Journal	Journal of Cancer Research and Clinical Oncology
Volume	144
Issue number	8
Pages (from-to)	1569-1580
ISSN	0171-5216
DOIs	https://doi.org/10.1007/s00432-018-2674-9
Publication status	Published - 1 Aug 2018

Keywords

Adolescent
Adult
Cohort Studies
DNA, Viral/blood
Epstein-Barr Virus Infections/blood
Female
Hematopoietic Stem Cell Transplantation/adverse effects
Herpesvirus 4, Human/genetics
Humans
Incidence
Lymphoproliferative Disorders/blood
Male
Middle Aged
Organ Transplantation/adverse effects
Retrospective Studies
Young Adult

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Wareham, N. E., Mocroft, A., Sengeløv, H., Da Cunha-Bang, C., Gustafsson, F., Heilmann, C., Iversen, M., Kirkby, N. S., Rasmussen, A., Sørensen, S. S., Lundgren, J. D., & MATCH in PERSIMUNE study group (2018). The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients. Journal of Cancer Research and Clinical Oncology, 144(8), 1569-1580. https://doi.org/10.1007/s00432-018-2674-9

The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients. / Wareham, Neval E; Mocroft, Amanda; Sengeløv, Henrik et al.
In: Journal of Cancer Research and Clinical Oncology, Vol. 144, No. 8, 01.08.2018, p. 1569-1580.

Research output: Contribution to journal › Journal article › Research › peer-review

Wareham, NE, Mocroft, A, Sengeløv, H, Da Cunha-Bang, C, Gustafsson, F, Heilmann, C, Iversen, M, Kirkby, NS, Rasmussen, A, Sørensen, SS , Lundgren, JD & MATCH in PERSIMUNE study group 2018, 'The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients', Journal of Cancer Research and Clinical Oncology, vol. 144, no. 8, pp. 1569-1580. https://doi.org/10.1007/s00432-018-2674-9

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title = "The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients",

abstract = "PURPOSE: Emerging EBV DNAemia in plasma is considered an early sign of post-transplant lymphoproliferative disorder (PTLD). The aim of this study was to quantify the extent of benefit from screening for EBV DNAemia to detect emerging PTLD among solid organ (SOT) or hematopoietic stem cell transplant recipients (HSCT).METHODS: We used receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD. Among 2642 recipients transplanted between January 2004 and December 2014, 79 (3%) developed PTLD.RESULTS: EBV DNAemia was observed in 331/1784 recipients (18.6%, 95% CI 16.8-20.4) with measured EBV DNA. The area under the curve (AUC) of the ROC of EBV DNAemia to identify persons with subsequent PTLD was 72% (95% CI, 64-79%) among SOT and 59% (51-68%) among HSCT. Including clinical predictors such as age, gender, transplant year and type, high-risk EBV serostatus, and routine biochemistry in addition to EBV DNAemia increased AUC to 83% (75-90%) among SOT and 84% (79-89%) among HSCT. Among HSCT, including additional factors such as T-cell-depleting treatment, acute graft vs. host disease and donor match increased AUC to 85% (78-91%).CONCLUSIONS: We constructed a model to better predict PTLD compared to EBV DNA screening alone which could have clinical implications.",

keywords = "Adolescent, Adult, Cohort Studies, DNA, Viral/blood, Epstein-Barr Virus Infections/blood, Female, Hematopoietic Stem Cell Transplantation/adverse effects, Herpesvirus 4, Human/genetics, Humans, Incidence, Lymphoproliferative Disorders/blood, Male, Middle Aged, Organ Transplantation/adverse effects, Retrospective Studies, Young Adult",

author = "Wareham, {Neval E} and Amanda Mocroft and Henrik Sengel{\o}v and {Da Cunha-Bang}, Caspar and Finn Gustafsson and Carsten Heilmann and Martin Iversen and Kirkby, {Nikolai S} and Allan Rasmussen and S{\o}rensen, {S{\o}ren Schwartz} and Lundgren, {Jens D} and {MATCH in PERSIMUNE study group}",

year = "2018",

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day = "1",

doi = "10.1007/s00432-018-2674-9",

language = "English",

volume = "144",

pages = "1569--1580",

journal = "Journal of Cancer Research and Clinical Oncology",

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TY - JOUR

T1 - The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients

AU - Wareham, Neval E

AU - Mocroft, Amanda

AU - Sengeløv, Henrik

AU - Da Cunha-Bang, Caspar

AU - Gustafsson, Finn

AU - Heilmann, Carsten

AU - Iversen, Martin

AU - Kirkby, Nikolai S

AU - Rasmussen, Allan

AU - Sørensen, Søren Schwartz

AU - Lundgren, Jens D

AU - MATCH in PERSIMUNE study group

PY - 2018/8/1

Y1 - 2018/8/1

N2 - PURPOSE: Emerging EBV DNAemia in plasma is considered an early sign of post-transplant lymphoproliferative disorder (PTLD). The aim of this study was to quantify the extent of benefit from screening for EBV DNAemia to detect emerging PTLD among solid organ (SOT) or hematopoietic stem cell transplant recipients (HSCT).METHODS: We used receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD. Among 2642 recipients transplanted between January 2004 and December 2014, 79 (3%) developed PTLD.RESULTS: EBV DNAemia was observed in 331/1784 recipients (18.6%, 95% CI 16.8-20.4) with measured EBV DNA. The area under the curve (AUC) of the ROC of EBV DNAemia to identify persons with subsequent PTLD was 72% (95% CI, 64-79%) among SOT and 59% (51-68%) among HSCT. Including clinical predictors such as age, gender, transplant year and type, high-risk EBV serostatus, and routine biochemistry in addition to EBV DNAemia increased AUC to 83% (75-90%) among SOT and 84% (79-89%) among HSCT. Among HSCT, including additional factors such as T-cell-depleting treatment, acute graft vs. host disease and donor match increased AUC to 85% (78-91%).CONCLUSIONS: We constructed a model to better predict PTLD compared to EBV DNA screening alone which could have clinical implications.

AB - PURPOSE: Emerging EBV DNAemia in plasma is considered an early sign of post-transplant lymphoproliferative disorder (PTLD). The aim of this study was to quantify the extent of benefit from screening for EBV DNAemia to detect emerging PTLD among solid organ (SOT) or hematopoietic stem cell transplant recipients (HSCT).METHODS: We used receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD. Among 2642 recipients transplanted between January 2004 and December 2014, 79 (3%) developed PTLD.RESULTS: EBV DNAemia was observed in 331/1784 recipients (18.6%, 95% CI 16.8-20.4) with measured EBV DNA. The area under the curve (AUC) of the ROC of EBV DNAemia to identify persons with subsequent PTLD was 72% (95% CI, 64-79%) among SOT and 59% (51-68%) among HSCT. Including clinical predictors such as age, gender, transplant year and type, high-risk EBV serostatus, and routine biochemistry in addition to EBV DNAemia increased AUC to 83% (75-90%) among SOT and 84% (79-89%) among HSCT. Among HSCT, including additional factors such as T-cell-depleting treatment, acute graft vs. host disease and donor match increased AUC to 85% (78-91%).CONCLUSIONS: We constructed a model to better predict PTLD compared to EBV DNA screening alone which could have clinical implications.

KW - Adolescent

KW - Adult

KW - Cohort Studies

KW - DNA, Viral/blood

KW - Epstein-Barr Virus Infections/blood

KW - Female

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Herpesvirus 4, Human/genetics

KW - Humans

KW - Incidence

KW - Lymphoproliferative Disorders/blood

KW - Male

KW - Middle Aged

KW - Organ Transplantation/adverse effects

KW - Retrospective Studies

KW - Young Adult

U2 - 10.1007/s00432-018-2674-9

DO - 10.1007/s00432-018-2674-9

M3 - Journal article

C2 - 29804164

SN - 0171-5216

VL - 144

SP - 1569

EP - 1580

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

IS - 8

ER -

The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients

Abstract

Keywords

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