mercaptopurine and Cognition-Disorders

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

In a multicenter study the authors prospectively investigated neurocognitive function in childhood ALL patients. Sixty-six patients (mean age at diagnosis 7.9 +/- 3.6 years, 34 female), treated with repeated intrathecal and systemical methotrexate administrations without cranial irradiation, underwent psychometric testing for intelligence, concentration, and visual-motor integration postdiagnosis and after reinduction therapy. Although there was a statistically significant decline of intellectual function after reinduction therapy for younger patients and girls (IQ scores still within normative data range), there were no differences in visual-motor performance and concentration over the time of induction therapy. Thus, neurocognitive examination should focus on younger ALL patients and girls.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cognition Disorders; Cranial Irradiation; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Follow-Up Studies; Humans; Injections, Spinal; Intelligence Tests; Longitudinal Studies; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prospective Studies; Psychomotor Performance; Risk Factors; Vincristine

To study, using serial neuropsychological assessment and evaluation of school achievement, persistent neuropsychological late effects in children treated for acute lymphoblastic leukemia (ALL) at a young age with chemotherapy only.. Twenty consecutive patients underwent three evaluations, including 12 psychometric measures beside IQ. The authors applied strict methodology and a prospective-longitudinal design that started at diagnosis and extended to a median follow-up of 7 years. This report focuses on the outcome of the last evaluation. Test results were compared with healthy controls and to patients with ALL treated on a previous chemotherapy-only protocol. School achievement was evaluated in patients and their siblings.. At the last evaluation, significantly lower test scores in patients compared with controls were found for only 2 of 14 cognitive measures (1 intelligence and 1 attention measure). No great differences were seen between school achievement of patients and siblings. Compared with the previous chemotherapy protocol, a better outcome was seen in the current study group on two measures (one memory and one attention measure).. Children surviving ALL have no major cognitive impairment after chemotherapy, including intrathecal and high-dose intravenous methotrexate. The slightly better outcome in the current group may indicate possible adverse effects of more dexamethasone treatment in the previous group.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Attention; Child, Preschool; Cognition Disorders; Cyclophosphamide; Cytarabine; Dexamethasone; Female; Follow-Up Studies; Humans; Ifosfamide; Injections, Spinal; Learning Disabilities; Longitudinal Studies; Male; Mercaptopurine; Methotrexate; Netherlands; Neuropsychological Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prospective Studies; Survivors; Teniposide; Treatment Outcome; Vincristine

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

Previous studies have failed to establish a direct relationship between behavioral disorders and organic pathology in long-term survivors of childhood acute lymphoblastic leukemia. We evaluated 23 long-term survivors who received central nervous system preventive therapy with cranial irradiation and intrathecal chemotherapy, using neuropsychologic tests and computed tomographic brain scans. The patients were in continuous first remission for 7 to 11 years, and none were receiving chemotherapy. On the basis of their CT scan findings, they were divided into three groups: 10 with normal CT findings, five with intracerebral calcifications, and eight with cortical atrophy. Neuropsychologic test results allowed prediction of CT scan findings with an 87% accuracy (P less than 0.001), indicating a strong correlation between the presence and type of CT scan abnormality and neuropsychologic functioning. Tests that measured verbal memory, attention, and functions correlated with frontal lobe integrity were most powerful in discriminating between groups.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cognition Disorders; Communication Disorders; Cytarabine; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Neuropsychological Tests; Prednisone; Tomography, X-Ray Computed; Vincristine