Molecular profiling and disease tracking of posttransplant lymphoproliferative disorders using cell-free DNA∗
8 affiliations
- 1Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- 2Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- 3Department of Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- 4Department of Hematology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- 5Department of Hematology, Erasmus University Medical Center, Erasmus University Rotterdam, Rotterdam, The Netherlands
- 6Department of Hematology, Maastricht University Medical Center, Maastricht University, Maastricht, The Netherlands
- 7Department of Hematology, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands
- 8Groningen Institute for Organ Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Abstract
Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of hematopoietic stem cell or solid organ transplantation. Current prognostic tools for PTLD lack sufficient precision in predicting treatment response. This prospective feasibility study evaluates circulating tumor DNA (ctDNA) for risk stratification and treatment monitoring in PTLD. Plasma samples (n = 86) from 27 patients (13 positive for Epstein-Barr virus [EBV] positive and 14 EBV negative) were analyzed using targeted 115-gene sequencing and low-coverage whole-genome sequencing at diagnosis, after rituximab treatment and/or chemotherapy, and at end of treatment (EOT). At baseline, somatic single-nucleotide variants were detected in all patients. Multinucleotide variants were mostly detected in the B-cell lymphoma 6 superenhancer hypermutation region, especially in EBV-negative patients. Copy number variants were detected in 13 of 27 patients. An elevated ctDNA level at baseline indicated a poor outcome of rituximab monotherapy, and an undetectable ctDNA level at interim was correlated with better response. Seven patients showed completely undetectable ctDNA levels, whereas positron emission tomography–computed tomography (PET/CT) scan indicated active disease at interim; all 7 patients reached complete metabolic response by EOT. We demonstrate that ctDNA could potentially be used for prognostication and disease monitoring in PTLD, outperforming PET/CT in 8 patients. This indicates that ctDNA monitoring can complement PET/CT to guide early escalation to chemotherapy in high-risk patients, although larger cohorts are needed to validate these findings. This trial was registered at the Dutch Trial Register as NTR7402.
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BibTeX
@article{zhong2026molecular,
title = {{Molecular profiling and disease tracking of posttransplant lymphoproliferative disorders using cell-free DNA∗}},
author = {Yujie Zhong and Nick Veltmaat and Filipe Montes de Jesus and Laurens Sillje and Rogier Mous and Martine E. D. Chamuleau and Sanne H. Tonino and Pim G. N. J. Mutsaers and Marjolein W. M. van der Poel and Wendy B. C. Stevens and Erik A. M. Verschuuren and Joost Kluiver and Anke van den Berg and Wouter J. Plattel and Arjan Diepstra and Marcel Nijland},
journal = {Blood Advances},
year = {2026},
month = aug,
doi = {10.1182/bloodadvances.2025018879},
url = {https://doi.org/10.1182/bloodadvances.2025018879},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Molecular profiling and disease tracking of posttransplant lymphoproliferative disorders using cell-free DNA∗
AU - Yujie Zhong
AU - Nick Veltmaat
AU - Filipe Montes de Jesus
AU - Laurens Sillje
AU - Rogier Mous
AU - Martine E. D. Chamuleau
AU - Sanne H. Tonino
AU - Pim G. N. J. Mutsaers
AU - Marjolein W. M. van der Poel
AU - Wendy B. C. Stevens
AU - Erik A. M. Verschuuren
AU - Joost Kluiver
AU - Anke van den Berg
AU - Wouter J. Plattel
AU - Arjan Diepstra
AU - Marcel Nijland
PY - 2026
DA - 2026/08/28
JO - Blood Advances
DO - 10.1182/bloodadvances.2025018879
UR - https://doi.org/10.1182/bloodadvances.2025018879
AB - Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of hematopoietic stem cell or solid organ transplantation. Current prognostic tools for PTLD lack sufficient precision in predicting treatment response. This prospective feasibility study evaluates circulating tumor DNA (ctDNA) for risk stratification and treatment monitoring in PTLD. Plasma samples (n = 86) from 27 patients (13 positive for Epstein-Barr virus [EBV] positive and 14 EBV negative) were analyzed using targeted 115-gene sequencing and low-coverage whole-genome sequencing at diagnosis, after rituximab treatment and/or chemotherapy, and at end of treatment (EOT). At baseline, somatic single-nucleotide variants were detected in all patients. Multinucleotide variants were mostly detected in the B-cell lymphoma 6 superenhancer hypermutation region, especially in EBV-negative patients. Copy number variants were detected in 13 of 27 patients. An elevated ctDNA level at baseline indicated a poor outcome of rituximab monotherapy, and an undetectable ctDNA level at interim was correlated with better response. Seven patients showed completely undetectable ctDNA levels, whereas positron emission tomography–computed tomography (PET/CT) scan indicated active disease at interim; all 7 patients reached complete metabolic response by EOT. We demonstrate that ctDNA could potentially be used for prognostication and disease monitoring in PTLD, outperforming PET/CT in 8 patients. This indicates that ctDNA monitoring can complement PET/CT to guide early escalation to chemotherapy in high-risk patients, although larger cohorts are needed to validate these findings. This trial was registered at the Dutch Trial Register as NTR7402.
SN - 2473-9529
SN - 2473-9537
ER -