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Neurological adverse events post allogeneic hematopoietic cell transplantation: major determinants of morbidity and mortality

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Abstract

Background

Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients.

Methods

We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center.

Results

Among 758 alloHCT recipients, 127 (16.8%) presented with neurological complications. Complications developed in central nervous system (89.7%) during the late post-transplant period. Neurological adverse events included a wide spectrum of infectious and non-infectious etiologies. With a median follow-up of 11.4 months, incidence of chronic graft-versus-host disease (GVHD) was 52.8%, relapse mortality 48.6%, transplant-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. Timing of appearance of neurological complications, early or late, was associated only with acute and chronic graft-versus-host-disease/GVHD. Independent pre-transplant risk factors of neurological complications in the multivariate model were unrelated or alternative donors, ALL diagnosis and non-myeloablative conditioning. In multivariate analysis of post-alloHCT events, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In our cohort, 10-year OS was significantly lower in patients with neurological complications and independently associated with acute and chronic GVHD, relapse, fungal and bacterial infections and neurological complications.

Conclusions

Our large study with long-term follow-up highlights the wide spectrum of neurological complications in alloHCT. Accurate recognition is required for adequate management, a major determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted.

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Acknowledgements

The authors thank Associate Professor in Medical Statistics-Epidemiology Anna Bettina Haidich for her contribution in the revised statistical analysis.

Funding

E.G. is supported by the European Hematology Association Clinical Research Grant 2016. The other authors have nothing to declare.

Author information

Authors and Affiliations

  1. BMT Unit, Hematology Department, G. Papanicolaou Hospital, Thessaloníki, Greece

    Ioanna Sakellari, Eleni Gavriilaki, Ioannis Batsis, Despina Mallouri, Anna Vardi, Varnavas Constantinou, Marianna Masmanidou, Evangelia Yannaki, Christos Smias & Achilles Anagnostopoulos

  2. 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloníki, Greece

    Sotirios Papagiannopoulos & Dimitrios Kazis

  3. Radiology Department, G. Papanicolaou Hospital, Thessaloníki, Greece

    Triantafyllos Geroukis

  4. School of Medicine, University Campus, Aristotle University of Thessaloniki, 54124, Thessaloníki, Greece

    Maria Gavriilaki & Vasileios Kimiskidis

  5. Laboratory of Clinical Neurophysiology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloníki, Greece

    Vasileios Kimiskidis

Authors
  1. Ioanna Sakellari
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  2. Eleni Gavriilaki
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  3. Sotirios Papagiannopoulos
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  4. Maria Gavriilaki
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  9. Marianna Masmanidou
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  12. Triantafyllos Geroukis
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  15. Achilles Anagnostopoulos
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Contributions

IS conceived and designed the study and drafted a significant portion of the manuscript. EG, SP and MG analyzed the data and drafted manuscript. IB, DM, AV, VC and MM acquired the data and drafted the tables and figures. AV, CM and TG participated in study conception and design and edited tables and figures. DK, VK and AA participated in study conception and design and edited the manuscript.

Corresponding author

Correspondence to Maria Gavriilaki.

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Conflicts of interest

There are no conflicts of interest to report.

Ethical standards

The study has been approved by the G. Papanicolaou Hospital ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Sakellari, I., Gavriilaki, E., Papagiannopoulos, S. et al. Neurological adverse events post allogeneic hematopoietic cell transplantation: major determinants of morbidity and mortality. J Neurol 266, 1960–1972 (2019). https://doi.org/10.1007/s00415-019-09372-3

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  • DOI: https://doi.org/10.1007/s00415-019-09372-3

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