Abstracts

Rationale: Hematopoietic stem cell transplantation (HSCT) is widely used as a treatment for patients with impaired bone marrow function. Despite significant improvements in HSCT procedures, neurological complications especially involving the central nervous system remain contributors to morbidity and mortality during the post-HSCT period. Since seizure is the most common clinical manifestation after HSCT, we assessed clinical profiles and risk factors of seizures to prevent seizures and improve the prognosis after HSCT.

Methods:
Patients and HSCT measurements:
Total of 554 children registered at Seoul St. Mary’s Hospital who received HSCT as treatment from January 2011 to January 2021 before the age of 18 were included in this study. Patients with a preexisting history of seizures before HSCT were excluded. Hematopoietic stem cells were classified into allogeneic cells harvested from donors and autologous cells harvested from patients themselves. All patients received pre-transplantation conditioning regimen including total body irradiation (TBI)-based, busulfan-based, TBI and busulfan-based, and others. As prophylaxis for graft versus host disease (GVHD), calcineurin inhibitors (cyclosporine, tacrolimus) with or without methotrexate (MTX), antithymoglobulin, and a steroid were administered.
_x000D_ Clinical profiles of seizures:
The timing of seizures was classified into three categories according to patient’s immune status after HSCT: < 30 days post-HSCT, 30 to 100 days post-HSCT and > 100 days post-HSCT. Abnormalities on electroencephalography (EEG) included background abnormalities and abnormal epileptiform discharges. The outcome of seizures included seizure freedom, development of epilepsy and death.

Results:
Demographic data and seizure profiles after HSCT (Table 1):
The incidence of HSCT-associated seizures was 6.2%. Seizures were most likely to develop 100 days after HSCT and generalized seizures tended to occur nearly twice as often as focal seizures. More than 70% and 80% of the patients who had seizures showed abnormal brain magnetic resonance imaging (MRI) and abnormal EEG results, respectively. About 70% of the seizure patients became seizure-free without requiring anti-seizure medication and 20% of patients developed epilepsy, whereas the remainder died during follow-up.
_x000D_ Risk factors for seizures after HSCT (Table 2):
- Type of HSCT - Patients receiving allogeneic transplants had higher risk of developing seizures than patients with autologous transplants (p=0.023)
- Prophylaxis regimen for GVHD - Patients using calcineurin inhibitors combined with MTX showed higher risk of developing seizures compared to patients with other regimens (p=0.006)
- Grade of acute GVHD - Patients with grade 2–4 acute GVHD had a higher risk of developing seizures than those with grade 0–1 acute GVHD (p=0.003)

Conclusions: Our results showed that children receiving allogeneic transplants and calcineurin inhibitors with MTX for GVHD prophylaxis, having high grade of acute GVHD were risk factors for seizures, all requiring higher dose, prolonged and cumulative immunosuppressant administration. Close observation and intensive management of seizures seem to be necessary to improve neurological outcomes.

Funding: Not applicable