A Review of Acute and Long-Term Neurological Complications Following Haematopoietic Stem Cell Transplant for Paediatric Acute Lymphoblastic Leukaemia

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.

Long-term toxicities after allogeneic hematopoietic stem cell transplantation with or without total body irradiation: a population-based study in Korea

“…However, although the reliability is low due to the small number of toxicity events, the IRR for stroke was increased after TBI in patients ≤ 47 years. Because the fol-low-up period of this study was not long enough, there may be differences between groups after sufficient follow-ups, in accordance with recent reviews that described a potential higher risk for stroke in older-aged patients after a TBI-conditioning regimen [25].…”

Conclusive demonstration of iatrogenic Alzheimer’s disease transmission in a model of stem cell transplantation

“…The majority of studies on the neurological effects of HSCT in children have focused on acute neurotoxicity, but, as more children undergoing HSCT for acute lymphoblastic leukemia become long-term survivors, understanding the long-term neurological consequences of this treatment modality is increasingly important. Radiotherapy and chemotherapy, as parts of HSCT treatment, can add to neurological injury and have profound effects on brain maturation and cognitive function ( Gabriel et al., 2021 ).…”

Viral meningoencephalitis in pediatric solid organ or hematopoietic cell transplant recipients: a diagnostic and therapeutic approach

“…Up to 46% of children who undergo hematopoietic cell transplantation (HCT) and 30%-50% pediatric solid organ transplant recipients experience neurological complications (Table 1). Among HCT recipients who experience neurological complications, a lower incidence reported in the first year post-transplant compared to later time points (1)(2)(3)(4)(5)(6). In an Israeli study spanning two decades and including more than 700 pediatric HCT recipients, non-infectious complications were found to be more common (81.3%) compared to infectious complications (18.7%) (7).…”