Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Early childhood caries: analysis of psychosocial and biological factors in a high-risk population.

The influences that link social factors and caries development are not well understood, although mediation by stress has been suggested. The association between caregiver stress and early childhood caries (ECC), in particular, remains unclear. The purpose of this study was to examine the relationships between parenting stress and ECC while controlling for behavioral and biological factors in a high-risk population. One hundred and fifty healthy children aged 18-36 months were examined in a cross-sectional study design. Parental interviews were conducted to obtain demographic, oral health behavior and parenting stress data. Clinical data included parent and child bacterial measures, fingernail fluoride analyses, caries prevalence and presence of child enamel hypoplasia. Bivariate analyses revealed that parenting stress predicted caries. Multivariate analyses demonstrated that a combination of psychosocial, behavioral, temporal and biological variables predicted ECC outcomes. Total parenting stress did not contribute independently to the best prediction model. Our findings suggest the need for the development of a multidimensional stress model that considers the parent-child dyad to elucidate further the link between psychosocial factors and ECC.

Outcome in children with fetal mild ventriculomegaly: a case series.

Mild enlargement of the lateral ventricles is associated with schizophrenia and other neurodevelopmental disorders. While it has been hypothesized that ventricle abnormalities associated with neurodevelopmental disorders arise during fetal brain development, there is little direct evidence to support this hypothesis. Using ultrasound, it is possible to image the fetal ventricles in utero. Fetal mild ventriculomegaly (MVM) has been associated with developmental delays in early childhood, though longer-term neurodevelopmental outcome has not been studied. Follow-up of five children (aged 4--9 years) with mild enlargement of the lateral ventricles on prenatal ultrasound and two unaffected co-twins is reported: one child had attention deficit hyperactivity disorder (ADHD), one had autism, and two had evidence of learning disorders. These cases suggest that the mild enlargement of the lateral ventricles associated with these neurodevelopmental disorders arises during fetal brain development and can be detected with prenatal ultrasound. In addition, the presence of mildly enlarged, asymmetric ventricles in two children on prenatal ultrasound and on follow-up MRI at age 6 years indicates that ventricle structure present in utero can persist well into childhood brain development. The study of fetal ventricle development with ultrasound may provide important insights into neurodevelopmental disorders and allow the identification of children at high risk.

Social skills and psychological adjustment of child and adolescent cancer survivors.

Social skills and psychological adjustment for survivors of childhood cancer were investigated. Cancer survivors included 42 children and adolescents ranging in age at evaluation from 6 to 18 years with a mean age of 13.1 years. Measures included teacher and parent ratings of social skills and adjustment and parent ratings of family functioning. The findings showed that social skills and psychological adjustment as rated by both parents and teachers were primarily associated with academic functioning. In addition, family cohesiveness was found to account for nearly one third of the variance in survivors' adjustment when rated by teachers, and length of time off treatment accounted for a significant percentage of the variance in children's adjustment when rated by parents. The findings underscore the importance of a multi-informant approach to the assessment of psychological adjustment of pediatric cancer survivors and demonstrate the role of learning difficulties and family functioning in influencing social skills and adjustment for these children and adolescents.

Neurodevelopmental outcome of infants with acute lymphoblastic leukemia: a Children's Cancer Group report.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

HIV-infected children with hemophilia: one- and two-year follow-up of neuropsychological functioning.

This report describes the absence of neuropsychologic change observed over a 2-year period for 25 HIV-seropositive (HIV+) children and adolescents with hemophilia and 33 HIV-seronegative (HIV-) controls. Efforts were made to match the groups on the basis of chronological age, race, and hemophilia severity. The baseline evaluation included blinded neuropsychologic measurement of motor, attention, language, visual processing, memory, and general intelligence. HIV+ and HIV-group means did not differ at baseline on any neuropsychologic domain, and this trend continued at the 2-year follow-up. Mixed models analyses did not indicate that the HIV+ group performed more poorly than the HIV- group on any of the neuropsychological domains, nor did they show different patterns of change over time on these variables for the HIV+ group. Consistent with emergent findings, it continues to be premature to attribute subtle neuropsychologic deficits in seropositive children with hemophilia directly to the central nervous system (CNS) effects of HIV infection.

Behavioral adjustment and social functioning of long-term survivors of childhood leukemia: parent and teacher reports.

Obtained parent and teacher reports of behavior and social competence for children who were survivors of acute lymphoblastic leukemia (ALL). At follow-up, children were 5-18 years of age, 48 months postdiagnosis, in first continuous remission, and off chemotherapy. Each child had been randomized to receive either 1,800 cGy whole brain radiation therapy (WBRT) plus intrathecal methotrexate (IT MTX), or IT MTX alone as central nervous system prophylaxis, and one of four chemotherapy regimens that varied in treatment intensity. Scores on standardized measures (CBCL-P/T and PIC) were generally similar to instrument norms. Parents, but not teachers, reported heightened child somatic concerns. There was no effect of WBRT or chemotherapy regimen on ratings of behavioral adjustment. Results indicate minimal psychosocial morbidity among long-term survivors of ALL and suggest that the stressful life events associated with cancer and its treatment do not cause significant behavioral or emotional difficulties.

MRI morphometric analysis and neuropsychological function in patients with neurofibromatosis.

Volumes of cerebral gray and white matter were measured in 22 children with neurofibromatosis type 1 (NF1) and in 20 controls. Judgment of Line Orientation (JLO) and the Developmental Test of Visual-Motor Integration (DTVMI) were administered to 16 of the NF1 patients. General linear models analysis of covariance revealed significantly larger brain volumes in NF1 children than in controls, particularly in white matter, and particularly in girls. JLO and DTVMI performance were positively related to right-hemisphere gray-matter volume. The results implicate a failure of growth control in NF1, leading to aberrant neurodevelopment. Our findings also suggest a basis for refined understanding of learning disabilities, which are a prominent feature of NF1.

Neuropsychological effects of cranial irradiation in young children with acute lymphoblastic leukemia 9 months after diagnosis. The Children's Cancer Group.

STUDY OBJECTIVE: To determine the effects of cranial irradiation on neuropsychological test performance evident 9 months after diagnosis. DESIGN: A companion study to a randomized clinical trial (CCG-105). SETTING: Institutions participating in Childrens Cancer Group cooperative treatment trials. PATIENTS: Seventy-four children aged 3.0 to 6.5 years with average-risk acute lymphoblastic leukemia. Children with central nervous system leukemia at the time of diagnosis, preexisting mental retardation, or Down's syndrome or for whom English was not the primary language were not eligible for study. INTERVENTIONS: Children were randomized to receive treatment with one of four systemic chemotherapy regimens and either intrathecal methotrexate sodium during induction and consolidation plus 18 Gy of cranial irradiation or intrathecal methotrexate during induction, consolidation, and maintenance as central nervous system prophylaxis. MEASUREMENT AND RESULTS: The groups were comparable with regard to chronologic age, sex, and family socioeconomic status. Children who received cranial irradiation plus intrathecal methotrexate scored significantly lower on the McCarthy Motor Scale (P < .05) and the Token Test (P < .05) than children who received intrathecal methotrexate alone. The groups did not differ significantly on the McCarthy General Cognitive Index, Developmental Test of Visual Motor Integration, or Peabody Picture Vocabulary Test-Revised. CONCLUSIONS: Findings suggest that the combined effects of cranial irradiation and intrathecal methotrexate therapy on neuropsychological performance may be evident in young children as early as 9 months after diagnosis. Follow-up assessment of these children will reveal whether these effects remain constant, intensify, or resolve.

Behavioral adaptation to human immunodeficiency virus-seropositive status in children and adolescents with hemophilia.

OBJECTIVE: To examine the behavioral adaptation to human immunodeficiency virus (HIV)-seropositive status, as defined by parental report, in children and adolescents with hemophilia. RESEARCH DESIGN: A clinical descriptive study of two groups of patients as part of a longitudinal design. SETTING: A university-based comprehensive hemophilia center and department of neurology acquired immunodeficiency syndrome dementia center. PATIENTS: Forty-six male children with hemophilia divided into two groups based on HIV-seropositive (n = 18) or -seronegative (n = 28) status. None of the patients were symptomatic for acquired immunodeficiency syndrome. SELECTION PROCEDURES: All pediatric patients with documented factor VII or IX deficiency aged between 4 and 19 years at study onset and their families were eligible to participate. All subjects were recruited without regard to human immunodeficiency virus status. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Profiles of behavioral adjustment were obtained from parents' reports on the Child Behavior Checklist for the HIV-seropositive and HIV-seronegative groups. The two groups did not differ on any of the major indexes of the Child Behavior Checklist, even after adjusting for maternal education and severity of hemophilia. There also was no difference between the groups when individual cases were examined for the number of child behavior checklist scales falling within a clinically significant range. CONCLUSIONS: The current findings fail to confirm any clear evidence of behavioral problems in an asymptomatic group of HIV-seropositive children and adolescents with hemophilia.

Neuropsychologic functioning of human immunodeficiency virus-infected children with hemophilia.

Efforts to detect subtle but objective neuropsychologic deficits could clarify the early involvement of the central nervous system and the progression of human immunodeficiency virus (HIV) infection in older children and young adolescents. Baseline examinations of 63 children and adolescents with hemophilia were conducted by examiners unaware of HIV status or staging or of our study's major hypotheses. They measured six domains of neuropsychologic functioning (motor, language, memory, attention, visual processing, and problem solving), and no differences between groups of similar age, race, and socioeconomic status defined by HIV seropositivity (n = 25) and HIV seronegativity (n = 38) were revealed. A high incidence of subtle neuropsychologic deficits relative to (1) age norms and (2) individual cognitive potential was found on measures of motor performance, attention, and speeded visual processing within both infected and uninfected groups. On the basis of these baseline data, it seems premature to attribute early, subtle neuropsychologic deficits in seropositive children with hemophilia to the central nervous system effects of HIV infection.

Neuropsychologic and academic functioning of children with sickle cell anemia.

This study compared neuropsychologic test results and academic functioning among 28 school-age children with sickle cell anemia (SCA), and 28 healthy, age-, sex-, and socioeconomically matched black peers followed at a tertiary care center. Children with SCA scored significantly lower on reading and spelling achievement scores than healthy matched peers. Also, older children with SCA performed significantly less well on tests of visual-motor and attention skills than younger children with SCA. These results were unrelated to most measures of physical illness severity. The data suggest that sickle cell anemia may be associated with subtle neuropsychological and learning deficits that can contribute to decreased school performance.

Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae.

A battery of neuropsychologic tests was administered "blindly" to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child.

Endorsements of Ellis' irrational beliefs as a function of DSM-III psychotic diagnoses.

Asked normal Ss (N = 120) as well as patients (N = 150) diagnosed as manic, major depressive disorder and schizophrenic to give their opinions with regard to Ellis' 11 irrational beliefs. The schizophrenia group and major depressive group were noted to endorse at least 3 and 4 of the irrational beliefs, respectively, a striking contrast to both the normal and manic groups, who did not endorse any of these ideas. Thus, the data with regard to two of the three psychotic groups are consistent with rational-emotive theory.

Utility of MMPI indices of schizophrenia with adolescents.

Assessed the utility of empirically derived MMPI criteria for the diagnosis of schizophrenia with a sample of hospitalized adolescent patients (N = 89). The criterion diagnosis was established through the use of a standardized structured interview and a diagnostic system for schizophrenia based on the use of discriminant function analysis. Results were quite disappointing because only 23% of the sample obtained an MMPI profile that fit the above criteria.

The mother-infant relationship and infant development: the effect of pediatric intervention.

This study examined the impact of intervention provided in the context of pediatric health supervision visits on the mother-infant relationship during the first 6 months of life. 32 mother-infant dyads were randomly assigned at birth to either an intervention or attention control group, each of which received routine well-child care plus discussions regarding infant social development or accident prevention and nutrition, respectively. Blind assessment of infant and mother behavior frequencies, responsive behavior sequences, and affective relationship characteristics during a 21-min play observation revealed more sensitivity, cooperativeness, appropriateness of interaction, and appropriateness of play by the intervention group pairs, although differences in Bayley Mental Scales and the Uzgiris and Hunt subscales did not attain significance. Post hoc inspection of the behavioral correlates of the affective relationship characteristics provided support for molar assessment of mother-infant interaction as an adjunct to contemporary methods of behavioral microanalytic study.