mercaptopurine and Movement-Disorders

Infants diagnosed with acute lymphoblastic leukemia (ALL) are considered the patient subgroup at the highest risk for central nervous system (CNS) disease, both at presentation and as an isolated extramedullary relapse. In addition, they are highly vulnerable to adverse developmental sequelae from CNS-directed therapy.. Thirty patients younger than 12 months at diagnosis (12 males, 18 females) in first hematologic remission were evaluated after completion of ALL therapy (mean age = 62.1 months; standard deviation = 17.2 months; range = 38-102 months). CNS-directed treatment included very high dose infusions of methotrexate (MTX) and intrathecal cytarabine and MTX. Three patients had meningeal leukemia that required additional therapy. Children were administered the McCarthy Scales of Children's Abilities, and parents completed a sociodemographic questionnaire to obtain information about occupation and education.. Mean scores on all 6 cognitive and motor indices of the McCarthy Scales were in the average range (Verbal = 52.0; Perceptual = 53.6; Quantitative = 49.6; General Cognitive Index [GCI] = 102.1; Memory = 49.2; Motor = 51.0). Score distributions for each neurodevelopmental index were comparable to age-based population standards. One patient obtained a GCI that exceeded 2 standard deviations above the mean; none scored more than 2 standard deviations below. There was no report of developmental disabilities or neurologic disorders for any of the patients. Risk factors, including age at diagnosis, gender, additional CNS-directed treatment, and family socioeconomic status, were not associated with developmental outcome.. Test findings indicated a generally positive neurodevelopmental outcome for ALL patients diagnosed in infancy who were treated with very high dose MTX as CNS-directed therapy. Combined with the reduction in the isolated CNS relapse rate achieved by the Children's Cancer Group (CCG) clinical trial CCG-107, the results of this study represent a substantial improvement in neurodevelopmental outcome for very young patients compared with infants treated for ALL in the past.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Brain Damage, Chronic; Cognition Disorders; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Developmental Disabilities; Female; Follow-Up Studies; Humans; Infant; Injections, Spinal; Leucovorin; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Movement Disorders; Neuropsychological Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Psychomotor Performance; Remission Induction; Risk; Socioeconomic Factors; Survivors; Vincristine

We report a 13-year-old boy with Lennox-Gastaut syndrome (LGS) associated with leukoencephalopathy. He was diagnosed with unclassified acute lymphocytic leukemia at the age of 3 years. After initial chemotherapy, he received intravenous methotrexate (total dosage 1,035 mg), intrathecal methotrexate (total dosage 221 mg), and whole brain irradiation (2,400 cGy). From about the age of 8 years, he developed slurred speech, hyperactivity, and mental deterioration. Cranial CT revealed calcification of the subcortical white matter. At age 9 years, he exhibited tonic seizures and atonic seizures. EEG showed diffuse slow spike-wave discharges, which are characteristic of LGS. Although multiple antiepileptic drugs have been prescribed, the frequency of seizures remains unchanged and his mental state is becoming progressively worse.

Topics: Adolescent; Anticonvulsants; Antineoplastic Combined Chemotherapy Protocols; Brain Damage, Chronic; Calcinosis; Cranial Irradiation; Cytarabine; Dementia; Doxorubicin; Electroencephalography; Epilepsy, Absence; Epilepsy, Generalized; Humans; Injections, Spinal; Male; Mercaptopurine; Methotrexate; Movement Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Radiation Injuries; Syndrome; Vincristine