Abstract

Despite advances in haematopoietic stem cell transplant (HSCT) techniques, the risk of serious side effects and complications still exists. Neurological complications, both acute and long term, are common following HSCT and contribute to significant morbidity and mortality. The aetiology of neurotoxicity includes infections and a wide variety of non-infectious causes such as drug toxicities, metabolic abnormalities, irradiation, vascular and immunologic events and the leukaemia itself. The majority of the literature on this subject is focussed on adults. The impact of the combination of neurotoxic drugs given before and during HSCT, radiotherapy and neurological complications on the developing and vulnerable paediatric and adolescent brain remains unclear. Moreover, the age-related sensitivity of the nervous system to toxic insults is still being investigated. In this article, we review current evidence regarding neurotoxicity following HSCT for acute lymphoblastic leukaemia in childhood. We focus on acute and long-term impacts. Understanding the aetiology and long-term sequelae of neurological complications in children is particularly important in the current era of immunotherapy for acute lymphoblastic leukaemia (such as chimeric antigen receptor T cells and bi-specific T-cell engager antibodies), which have well-known and common neurological side effects and may represent a future treatment modality for at least a fraction of HSCT-recipients.

Highlights

  • Neurological complications occurring post paediatric haematopoietic stem cell transplantation (HSCT) contribute significantly to morbidity and mortality both in the short and long term

  • We review the risk of posterior reversible encephalopathy, which is most commonly associated with calcineurin inhibitors used for graft-vs.-host disease (GvHD) prophylaxis in the majority of patients undergoing HSCT

  • We have provided a comprehensive review of both the acute and long-term neurological complications in children following HSCT for acute lymphoblastic leukaemia (ALL)

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Summary

INTRODUCTION

Neurological complications occurring post paediatric haematopoietic stem cell transplantation (HSCT) contribute significantly to morbidity and mortality both in the short and long term. The incidence of neurotoxicity in children following HSCT, for a variety of indications, ranges in the literature from 11–59% [1,2,3,4,5,6]. There is a paucity of literature examining neurological complications in children undergoing HSCT for ALL

Neurotoxicity in Paediatric ALL HSCT
Risk factors
Neurocognitive effects Fatigue Decreased HRQoL
Infectious Causes of Acute Neurotoxicity
Cerebrovascular Accidents
Secondary CNS Malignancies Post HSCT
Peripheral Neuropathy Post HSCT
Impact on Cognition
NEUROTOXICITY SYNDROME
Findings
CONCLUSION
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