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Reduction of immunosuppression combined with whole-brain radiotherapy and concurrent systemic rituximab is an effective yet toxic treatment of primary central nervous system post-transplant lymphoproliferative disorder (pCNS-PTLD): 14 cases from the prospective German PTLD registry

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Abstract

Post-transplant lymphoproliferative disorders (PTLD) exclusively affecting the central nervous system—primary CNS-PTLD (pCNS-PTLD)—are rare. There is no standard therapy, and previous case series have included heterogeneous treatment approaches. We performed a retrospective, multi-centre analysis of 14 patients with pCNS-PTLD after solid organ transplantation (SOT) treated in the prospective German PTLD registry with reduction of immunosuppression (RI), whole-brain radiotherapy (WBRT), and concurrent systemic rituximab between 2001 and 2018. Twelve of fourteen patients were kidney transplant recipients and median age at diagnosis was 65 years. Thirteen of fourteen cases (93%) were monomorphic PTLD of the diffuse large B-cell lymphoma type, and 12/13 were EBV-associated. The median dose of WBRT administered was 40 Gy with a median fraction of 2 Gy. The median number of administered doses of rituximab (375 mg/m2) IV was four. All ten patients evaluated responded to treatment (100%). Median OS was 2.5 years with a 2-year Kaplan–Meier estimate of 63% (95% confidence interval 30–83%) without any recorded relapses after a median follow-up of 2.6 years. Seven of fourteen patients (50%) suffered grade III/IV infections under therapy (fatal in two cases, 14%). During follow-up, imaging demonstrated grey matter changes interpreted as radiation toxicity in 7/10 evaluated patients (70%). The combination of RI, WBRT, and rituximab was an effective yet toxic treatment of pCNS-PTLD in this series of 14 patients. Future treatment approaches in pCNS-PTLD should take into account the significant risk of infections as well as radiation-induced neurotoxicity.

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Funding

The German PTLD registry has been supported through a grant from Roche Germany.

Author information

Authors and Affiliations

  1. Department of Haematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Gröpelinger Heerstr. 406-408, 28239, Bremen, Germany

    Heiner Zimmermann & Ralf U. Trappe

  2. Center of Radiotherapy, Bremen, Germany

    Mirko Nitsche & Robert M. Hermann

  3. Department of Internal Medicine II: Haematology and Oncology, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Christiane Pott, Matthias Ritgen & Ralf U. Trappe

  4. Department of Nephrology and Intensive Care, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Petra Reinke

  5. Center for Translational Medicine and Department of Internal Medicine I, Marien Hospital Herne, Ruhr-University Bochum University Hospital, Herne, Germany

    Nina Babel

  6. Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany

    Robert M. Hermann

  7. Department of Nephrology, UKF, Goethe University Frankfurt, Frankfurt/Main, Germany

    Ingeborg A. Hauser

  8. Department of Haematology, Oncology and Palliative Care, Katharinen hospital, Stuttgart, Germany

    Dennis Hahn

  9. Radiologie Bremen, Bremen, Germany

    Claudia Pietschmann

  10. Department of Haematopathology, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Wolfram Klapper

  11. Department of Pathology, University of Würzburg, Würzburg, Germany

    Ioannis Anagnostopoulos

  12. Department of Haematology and Oncology, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Ralf U. Trappe

Authors
  1. Heiner Zimmermann
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  2. Mirko Nitsche
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  3. Christiane Pott
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  4. Petra Reinke
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  8. Dennis Hahn
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Consortia

for the German PTLD Study Group and German Lymphoma Alliance

Contributions

HZ, MN, and RUT designed the study. RUT is the principal investigator and takes primary responsibility for the paper. HZ, MN, CP, PR, NB, RMH, IAH, DH, MR, and RUT recruited and treated significant numbers of patients. HZ, MN, and RUT collected, analyzed, and interpreted the data. CP performed, analyzed, and collated radiology studies. MR performed reference flow cytometry. WK and IA performed reference haematopathology. HZ, MN, and RUT wrote the paper. All authors had full access to the final version of the manuscript and agreed to publication.

Corresponding author

Correspondence to Ralf U. Trappe.

Ethics declarations

Ethics approval

The German PTLD registry was approved by the appropriate Ethics committees.

Consent to participate

Patients provided informed consent to the German PTLD registry according to the Declaration of Helsinki.

Conflict of interest

Dr. Zimmermann reports institutional grants from Atara and Roche, and travel support from Atara, Celgene, and Jansen, outside the submitted work. Dr. Hauser reports personal fees or travel support from Astellas, Biotest, Hexal, Neovii, Novartis, and Roche, all outside the submitted work. Dr. Ritgen reports personal fees from Hoffman LaRoche, AbbVie, AstraZeneca, and Jansen, all outside the submitted work. Claudia Pietschmann reports travel support by KS Pharma, outside the submitted work. Dr. Trappe reports institutional grants from Atara and Roche and non-financial support from Roche, Atara, Celgene, Janssen, and AbbVie, all outside the submitted work. All other authors declare no competing interests.

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Zimmermann, H., Nitsche, M., Pott, C. et al. Reduction of immunosuppression combined with whole-brain radiotherapy and concurrent systemic rituximab is an effective yet toxic treatment of primary central nervous system post-transplant lymphoproliferative disorder (pCNS-PTLD): 14 cases from the prospective German PTLD registry. Ann Hematol 100, 2043–2050 (2021). https://doi.org/10.1007/s00277-021-04548-2

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