mercaptopurine and Seizures

Limited information is available regarding neurocognitive outcomes of children who experience seizures during treatment for acute lymphoblastic leukemia (ALL). Accordingly, the main objectives of this study were to determine the incidence and risk factors for treatment-related seizures among children with ALL, and the neurocognitive outcomes associated with treatment-related seizures.. Prospective neuropsychological assessment and magnetic resonance imaging (MRI) were planned for all 498 patients with newly diagnosed ALL enrolled on the St. Jude Total Therapy XV (TOTXV) protocol at three time points. The study database was reviewed retrospectively to identify those with treatment-related seizure. To assess neurocognitive changes associated with seizure, each patient with treatment-related seizure was matched with two cohort patients without seizure for age at treatment, gender, race, and treatment intensity.. Nineteen patients developed seizure, with a 2-year cumulative risk of 3.82 ± 0.86% (SE). No risk factors were identified to be associated with the development of seizure, with a possible exception of intensive chemotherapy used on the standard/high-risk arm as compared to the low-risk arm. Neuropsychological performance of the seizure group, as compared to normative scores and nonseizure control cohort, indicated problems in attention, working memory, and processing speed. Cognitive deficits persisted 2 years after therapy, with additional declines in intellectual function observed. MRI indicated early neurotoxicity among the seizure group, as evidenced by greater leukoencephalopathy on initial examinations.. Treatment-related seizures were associated with leukoencephalopathy and decreased neuropsychological performance. Prospective studies are needed to detect changes in neurocognitive status associated with long-term functional impairment.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cognition Disorders; Cytarabine; Dexamethasone; Female; Humans; Hydrocortisone; Incidence; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Mercaptopurine; Methotrexate; Neuropsychological Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Seizures; Vincristine

A 4-year-old boy with acute lymphoblastic leukemia who was receiving 6-mercaptopurine during the maintenance chemotherapy experienced prolonged generalized tonic nocturnal seizures because of severe hypoglycemia after his evening dose by a 12-hour period of fasting. Investigations ruled out all causes of these seizures other than the 6-mercaptopurine-induced severe hypoglycemia.

Topics: Anti-Infective Agents; Antimetabolites, Antineoplastic; Child, Preschool; Humans; Hypoglycemia; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Seizures; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimetabolites, Antineoplastic; Burkitt Lymphoma; Child; Humans; Male; Mercaptopurine; Methotrexate; Piperacillin; Pseudomonas Infections; Seizures; Sepsis; Staphylococcal Infections

Methotrexate (MTX) and mercaptopurine (MP) are the mainstays of continuation therapy for acute lymphocytic leukemia (ALL). These drugs are stored in tissues as active metabolites. Relapse in ALL might reflect failure to achieve adequate intracellular drug levels. Assured (parenteral) delivery of higher doses of MTX and MP should maximize tissue levels of these drugs by overcoming individual variations in absorption, metabolism, clearance, and compliance. Fifty-nine children with ALL at lower risk of relapse received 12 intensive MTX/MP courses immediately after 4 weeks of standard vincristine, prednisone, and asparaginase induction. Each 2-week intensive course included: MTX, 200 mg/m2 intravenous (IV) push then 800 mg/m2 IV over 24 hours on day 1; MP, 200 mg/m2 IV push then 800 mg/m2 IV over 8 hours on day 2; MTX, 20 mg/m2 intramuscularly on day 8; and MP, 50 mg/m2 orally daily on days 8 to 14. After the 6 months of intensive therapy, continuation therapy was weekly MTX/MP (as on days 8 to 14) for 1 or 2 years. Age-based MTX was given intrathecally (IT) for CNS prophylaxis. All patients entered remission. Three patients relapsed: bone marrow (at 24 and 37 months), and bone marrow and CNS (at 34 months). There were no isolated CNS relapses or deaths in remission. Event-free survival at 4 years is 94% (SE, 7%) by Kaplan-Meier analysis. Toxicities (infection, mucositis) occurred in less than 10% of intensive MTX/MP courses. However, a child with Down's syndrome withdrew after three courses because of recurrent severe mucositis. Further studies of this regimen are in progress.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Male; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Seizures

Topics: Adult; Blood Transfusion; Brain; Brain Neoplasms; Cerebral Angiography; Cerebrovascular Disorders; Choriocarcinoma; Dactinomycin; Encephalitis; Female; Headache; Hemiplegia; Humans; Mercaptopurine; Methotrexate; Middle Aged; Neoplasm Metastasis; Neurologic Manifestations; Pregnancy; Seizures; Uterine Neoplasms

Topics: Adolescent; Adult; Azathioprine; Chlorambucil; Chronic Disease; Glomerulonephritis; Humans; Immunosuppressive Agents; Indomethacin; Kidney; Mercaptopurine; Middle Aged; Peritoneal Dialysis; Potassium; Prednisone; Prognosis; Proteinuria; Seizures; Time Factors

Topics: Brain Diseases; Carbohydrates; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Cranial Nerves; Folic Acid Antagonists; Headache; Hematocrit; Humans; Injections; Injections, Spinal; Leukemia; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone; Seizures; Toxicology

Topics: Child; Drug Hypersensitivity; Hypersensitivity; Mercaptopurine; Phenytoin; Prednisolone; Seizures; Toxicology