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Seizures in childhood lymphoblastic leukaemia patients
Insights
Children with acute lymphoblastic leukemia (ALL) receiving certain central nervous system (CNS) prophylaxis treatments, particularly repeated intrathecal methotrexate, face a significantly higher risk of seizures. This highlights a critical link between ALL treatment protocols and neurological side effects.
Area of Science:
- Pediatric Oncology
- Neurology
- Pharmacology
Background:
- Seizures are a potential complication in children undergoing treatment for acute lymphoblastic leukemia (ALL).
- The type of central nervous system (CNS) prophylaxis administered is suspected to influence seizure occurrence.
Purpose of the Study:
- To investigate the relationship between different CNS prophylaxis strategies and the incidence of seizures in pediatric ALL patients.
- To identify specific treatment-related factors associated with an increased risk of seizures.
Main Methods:
- Retrospective analysis of 1289 children with ALL, examining seizure history in relation to CNS prophylaxis received.
- Comparison of seizure rates based on varying intrathecal methotrexate schedules, intravenous methotrexate dosage, and cranial irradiation.
Main Results:
- 10% of patients experienced seizures, often generalized or focal motor without clear etiology.
- Higher seizure risk was observed with repeated intrathecal methotrexate, especially when combined with intravenous methotrexate or cranial irradiation.
- Escalated intravenous methotrexate post-irradiation and intrathecal methotrexate for meningeal leukemia were associated with increased seizure frequency.
Conclusions:
- Parenteral methotrexate administration appears to elevate seizure susceptibility in pediatric ALL patients.
- Specific CNS prophylaxis regimens, particularly those involving frequent intrathecal methotrexate, significantly increase seizure risk.
- Treatment strategies for ALL require careful consideration of neurological side effects like seizures.
Abstract:
Features of seizures in children with acute lymphoblastic leukaemia were examined in relation to the type of treatment received for central nervous system prophylaxis. Of the 1289 patients in the study, 132 (10%) had experienced one or more seizures. In 96 the seizures had not been associated with any recognisable aetiology and, with 3 exceptions, had been generalised or focal motor in type. Status epilepticus had occurred in one-third of the group with seizures. Initial seizure rates among patients in continuous complete remission were significantly related to the method of central nervous system prophylaxis. Those who had received intrathecal methotrexate repeatedly with or without moderate doses of methotrexate intravenously or prior prophylactic cranial irradiation had a 20-fold higher seizure risk during remission induction, and a 37-fold higher risk during the 6th to 12th month of therapy, than did those who had received irradiation and only five intrathecal injections of methotrexate early in the course of treatment. Other clinical factors associated with an increased frequency of seizures were escalation of intravenous methotrexate dosage following cranial irradiation and treatment of meningeal leukaemia with intrathecal methotrexate. Parenterally administered methotrexate thus seems to increase susceptibility to seizure development in childhood leukaemia patients.