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Central nervous system complications after allogeneic haematopoietic cell transplantation: best practice recommendations from the EBMT practice harmonisation and guidelines committee on epidemiology, outcome and neuroimaging

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Abstract

CNS complications (CNSC) may occur in a significant proportion of patients after allogeneic haematopoietic cell transplantation (allo-HCT). They can be differentiated into infectious and non-infectious CNSC, such as vascular pathologies (e.g., bleeding, stroke), drug-related abnormalities, and CNS relapse of the underlying malignancy. Initiation of prompt and adequate diagnostics – mainly neuroimaging and cerebrospinal fluid (CSF) analyses – and treatment are crucial to improve the prognosis. Here, we report on the epidemiology, outcome, and neuroimaging of CNSC after allo-HCT. We also provide an overview of the special considerations for children with these complications. These findings and recommendations were developed during a multidisciplinary EBMT harmonisation workshop. Novel diagnostics, such as CSF next-generation sequencing (NGS) and special MRI sequences, are emerging and may improve the accuracy of diagnosis for selected CNSC. The prognosis of post-transplant CNSC is heterogeneous, with drug-related CNSC mainly having a favourable prognosis, while the outcome of CNS bleeding, CNS leukaemia, and cerebral fungal disease is still frequently dismal. A high level of awareness is crucial in the clinical routine – especially in distinct subgroups such as paediatrics – besides the development of novel algorithms, diagnostics, and treatment approaches to improve the outcome.

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Fig. 1: Imaging approach to neurological complications after allogeneic haematopoietic cell transplantation.
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Acknowledgements

MSH thanks C. Theiler for editorial support. RV has received support from the Instituto de Salud Carlos III through the project PI24/01279 cofunded by the European Union and the Health Research and Innovation Strategic Plan (PERIS), Generalitat de Catalunya (Grant SLT042/25/000013). RV thanks the CERCA Programme/Generalitat de Catalunya for institutional support. OP acknowledges the support of José Carreras Leukämie-Stiftung (23 R/2021), Deutsche Krebshilfe (70113519), Deutsche Forschungsgemeinschaft (PE 1450/7-1, PE 1450/9-1, PE 1450/10-1, PE 1450/11-1) and Stiftung Charité BIH (BIH_PRO_549, Focus Group Vascular Biomedicine). ABR is supported by a Juan Rodés grant (JR24/00028) from the Instituto de Salud Carlos III, Spain. CB is a member of the European Reference Network for Neuromuscular Diseases. HS acknowledges the support of the UZ Leuven Klinische onderzoeks- en opleidingsraad (KOOR) of the University Hospitals of Leuven, Belgium. This manuscript was written by human without generative AI use.

Funding

The European Group for Blood and Bone Marrow transplantation (EBMT) is a non-profit medical and scientific organisation. The EBMT performed administrative and legal management, as well as funding acquisition. No pharmaceutical company and no other funding source were involved in any way or had a role in the study design, data collection, data analysis, data interpretation, or writing of the report. No medical writer or editor was involved.

Author information

Author notes

  1. These authors contributed equally: Martin Schmidt-Hieber, Roser Velasco.

Authors and Affiliations

  1. Clinic for Oncology, Haematology, Pneumology, Nephrology and Diabetology, Medical University Lausitz – Carl Thiem (MUL-CT), Cottbus, Germany

    Martin Schmidt-Hieber

  2. Infectious Diseases Working Party, EBMT, Leiden, Netherlands

    Martin Schmidt-Hieber, Dina Averbuch, Francesco Baccelli, Simone Cesaro, Rafael de la Cámara, Thushan de Silva, Per Ljungman, Malgorzata Mikulska, David Navarro, Dionysios Neofytos, José Luis Piñana & Jan Styczynski

  3. Department of Neurology, Neuro-oncology Unit, Institut Català d’Oncologia - Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain

    Roser Velasco

  4. Transplant Complications Working Party, EBMT, Paris, France

    Roser Velasco, Olaf Penack & Zinaida Perić

  5. Department of Cell Biology, Physiology, and Immunology, Universitat Autònoma de Barcelona, Bellaterra & CIBERNED, Barcelona, Spain

    Roser Velasco

  6. Department of Haematology, Oncology and Tumour Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Olaf Penack

  7. National Center for Tumour Diseases, Berlin, Germany

    Olaf Penack

  8. Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

    Dina Averbuch

  9. Hadassah Medical Center, Jerusalem, Israel

    Dina Averbuch

  10. Department of Haematology, Hospital Universitari I Politècnic la Fe, València, Spain

    Aitana Balaguer-Roselló

  11. Paediatric Haematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Francesco Baccelli

  12. Department of Neurology, Instituto Valenciano de Oncología, Department of Medicine, University of Valencia, Valencia, Spain

    Luis Bataller

  13. Paediatric Haematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

    Simone Cesaro

  14. Department of Neurosciences, Neurology Unit, University of Padova, Padova, Italy

    Chiara Briani

  15. Haematology Department, Hospital de la Princesa, Madrid, Spain

    Rafael de la Cámara

  16. Department of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Petra Huehnchen

  17. Berlin Institute of Health (BIH) at Charité – Universitätsmedizin Berlin, Berlin, Germany

    Petra Huehnchen

  18. NeuroCure Cluster of Excellence, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Petra Huehnchen

  19. Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK

    Thushan de Silva

  20. Clinical Haematology Department, Institut Català d’Oncologia, Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain

    Alberto Mussetti

  21. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Comprehensive Cancer Center, Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden

    Per Ljungman

  22. Department of Medicine Huddinge, Karolinska Institutet (KI), Stockholm, Sweden

    Per Ljungman

  23. Department of Haematology, University Hospital Centre Rijeka, Faculty of Medicine, University of Rijeka, Rijeka, Croatia

    Zinaida Perić

  24. Division of Infectious Diseases, Department of Health Sciences (DISSAL), University of Genova, Genova, Italy

    Malgorzata Mikulska

  25. IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Malgorzata Mikulska

  26. R.M. Gorbacheva Research Institute, Pavlov University, St Petersburg, Russia

    Alexey Polushin

  27. Department of Microbiology. Hospital Clínico Universitario of Valencia, Spain. INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain

    David Navarro

  28. Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain

    David Navarro

  29. Department of Neuroradiology, Neuro-oncology Unit, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute, Barcelona, Spain

    Albert Pons-Escoda

  30. Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland

    Dionysios Neofytos

  31. Department of Haematology, University Hospitals Leuven, Leuven, Belgium

    Hélène Schoemans

  32. Department of Public Health and Primary Care, ACCENT VV, KU Leuven - University of Leuven, Leuven, Belgium

    Hélène Schoemans

  33. Department of Haematology. Hospital Clínico Universitario of Valencia, Spain. INCLIVA, Biomedical Research Institute, Valencia, Spain

    José Luis Piñana

  34. Practice Harmonisation and Guidelines Committee, EBMT, Barcelona, Spain

    Francesco Onida, Annalisa Ruggeri, Isabel Sanchez-Ortega & Ibrahim Yakoub-Agha

  35. Haematology and BMT Unit, ASST Fatebenefratelli-Sacco, Department of Oncology and Haemato-Oncology, University of Milan, Milan, Italy

    Francesco Onida

  36. Cellular Therapy & Immunobiology Working Party, EBMT, Leiden, Netherlands

    Annalisa Ruggeri

  37. Haematology and BMT Unit, San Raffaele Scientific Institute, Milan, Italy

    Annalisa Ruggeri

  38. Medical Officer, EBMT, Executive Office, EBMT, Barcelona, Spain

    Isabel Sanchez-Ortega

  39. Centre Hospitalier Universitaire de Lille, University of Lille, INSERM U1286, Lille, France

    Ibrahim Yakoub-Agha

  40. Department of Paediatric Haematology, Oncology, Immunology and Transplantology, Collegium Medicum, Nicolaus Copernicus University Torun, University Hospital, Bydgoszcz, Poland

    Jan Styczynski

Authors
  1. Martin Schmidt-Hieber
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  2. Roser Velasco
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  3. Olaf Penack
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  13. Alberto Mussetti
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  14. Per Ljungman
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  15. Zinaida Perić
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  16. Malgorzata Mikulska
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  17. Alexey Polushin
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  18. David Navarro
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  19. Albert Pons-Escoda
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  20. Dionysios Neofytos
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  23. Francesco Onida
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  24. Annalisa Ruggeri
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  25. Isabel Sanchez-Ortega
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  26. Ibrahim Yakoub-Agha
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  27. Jan Styczynski
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Contributions

MSH, RV, OP, DA, and JS conceptualised the review and developed the methodology according to the EBMT practice and guidelines committee. All authors contributed to the literature search. MSH, RV, APE and JS screened and selected the included studies and extracted key data. MSH, RV, APE and JS wrote the first draft. IY-A formatted the final draft. All authors contributed to the interpretation of the evidence and edited subsequent versions. MSH, RV, OP, DA, and JS supervised the project and provided critical revisions. All authors approved the submitted manuscript and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Martin Schmidt-Hieber.

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Competing interests

DA: Speaker Takeda, MSD. DN: Conference fees: bioMérieux, Abbott Diagnostics. HS: Received personal fees from Incyte, Novartis, MAAT Pharma, Mallinckrodt Pharmaceuticals, Sanofi, BeiGene and the Belgian Haematological Society (BHS), as well as research funding from Sanofi, all paid to her institution and not directly related to this work. She has also received non-financial support from Pfizer, Sanofi, AbbVie, the EBMT, the IACH (International Academy for Clinical Haematology) and the CIBMTR (Center for International Bone Marrow Transplantation Research). JS: Participated in advisory boards for AstraZeneca, Moderna, MSD; and has been a speaker for Gilead, MSD, Roche and AstraZeneca. The other authors declare no competing financial interests related to this work.

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Schmidt-Hieber, M., Velasco, R., Penack, O. et al. Central nervous system complications after allogeneic haematopoietic cell transplantation: best practice recommendations from the EBMT practice harmonisation and guidelines committee on epidemiology, outcome and neuroimaging. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02869-2

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