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Central nervous system disorders after hematopoietic stem cell transplantation: a prospective study of the Infectious Diseases Working Party of EBMT

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Abstract

We performed a prospective study to evaluate the types and characteristics of central nervous system (CNS) disorders in patients after hematopoietic stem cell transplantation. The study included 163 episodes of CNS disorders of which 58 (36%) were infections. Proven or probable infections were documented in 34 patients and included fungi (n = 10, 29%), viruses (n = 12, 35%), Toxoplasma spp. (n = 9, 27%) and bacteria (n = 3, 9%). Non-infectious neurological disorders (n = 105, 64%) frequently encompassed metabolic/drug-induced abnormalities (n = 28, 27%) or cerebral vascular events (n = 22, 21%). Median onset times were later for infectious (day + 101) vs non-infectious neurological disorders (day + 50, p = 0.009). An unremarkable cranial CT scan was found in 33% of infection episodes. Absence of cerebrospinal fluid pleocytosis despite a normal or increased peripheral blood white blood cell count occurred in 26% of infections. Day-30 mortality rates were significantly higher for fungal (87%) vs non-fungal infections (40%, p < 0.001). Significantly higher mortality rates were also documented for cerebral vascular events than for other non-infectious disorders (86% vs 34%, p < 0.001). Our prospective study shows that diagnostic findings in CNS infections might differ between hematopoietic stem cell transplant recipients and immunocompetent hosts. Special awareness and timely initiation of adequate diagnostics are crucial to improve the prognosis of these patients.

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Authors and Affiliations

  1. Clinic for Hematology and Oncology, Carl-Thiem-Klinikum, Thiemstr. 111, 03048, Cottbus, Germany

    Martin Schmidt-Hieber

  2. Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Dan Engelhard

  3. Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany

    Andrew Ullmann & Hermann Einsele

  4. Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden

    Per Ljungman

  5. Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium

    Johan Maertens

  6. Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

    Rodrigo Martino

  7. Department of Hematology, Institute of Hematology and Oncology, IDIBAPS, Hospital Clinic, University of Barcelona, Josep Carreras Leukemia Research Institute, Barcelona, Spain

    Montserrat Rovira

  8. The Children’s Hospital at Westmead, Sydney, Australia

    Peter J. Shaw

  9. Assistance Publique-Hopitaux de Paris, Henri Mondor University Hospital, Hematology Department and UPEC, Créteil France Hôspital Henri Mondor, Créteil, France

    Christine Robin

  10. Hematopoietic Stem Cell Unit Transplantation, IRCCS Instituto G. Gaslini, Genova, Italy

    Maura Faraci

  11. Nottingham University Hospital, Nottingham, UK

    Jenny Byrne

  12. Clinic for Hematology and Oncology, Klinikum Nürnberg, Paracelsus Medizinische Privatuniversität, Nürnberg, Germany

    Kerstin Schäfer-Eckart

  13. Department of Hemato-Oncology, Faculty Hospital Olomouc, Faculty of Medicine and Dentistry Palacky University, Olomouc, Czech Republic

    Edgar Faber

  14. Ospedale S. Camillo, Rome, Italy

    Luigi Rigacci

  15. Azienda Ospedaliera Universitaria Careggi, Florence, Italy

    Riccardo Saccardi

  16. Hospital Universitari I Politècnic La Fe, Valencia, Spain

    Aitana Balaguer-Rosello

  17. Umea University Hospital, Umeå, Sweden

    Cecilia Isaksson

  18. Department of Stem Cell Transplantation, University Medical Center Eppendorf, Hamburg, Germany

    Maximilian Christopeit

  19. Pediatric Hematology Oncology, Mother and Child Hospital, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

    Gloria Tridello & Simone Cesaro

  20. EBMT Data Office, Leiden, The Netherlands

    Gloria Tridello, Junfeng Wang & Nina Knelange

  21. Division of Infectious Diseases, University of Genova, DISSAL, Genoa, Italy

    Malgorzata Mikulska

  22. IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Malgorzata Mikulska

  23. Department of Pediatric Hematology and Oncology, Collegium Medicum UMK, Bydgoszcz, Poland

    Jan Styczynski

Authors
  1. Martin Schmidt-Hieber
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Contributions

AU and DE designed the research. MSH, DE, AU, PL, JM, RM, MR, PJS, CR, MF, JB, KSE, HE, EF, LR, RS, ABR, CI, MC, GT, JW, NK, MM, SC and JS provided important clinical data and/or performed statistical analyses. MSH wrote the first draft of the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Martin Schmidt-Hieber.

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Conflicts of interest

MSH received travel support from the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). The other authors declared no conflicts of interest.

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Schmidt-Hieber, M., Engelhard, D., Ullmann, A. et al. Central nervous system disorders after hematopoietic stem cell transplantation: a prospective study of the Infectious Diseases Working Party of EBMT. J Neurol 267, 430–439 (2020). https://doi.org/10.1007/s00415-019-09578-5

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