Eighty-nine patients with untreated primary neuroblastomas were studied to determine the relation between the number of copies of the N-myc oncogene and survival without disease progression. Genomic amplification (3 to 300 copies) of N-myc was detected in 2 of 16 tumors in Stage II, 13 of 20 in Stage III, and 19 of 40 in Stage IV; in contrast, 8 Stage I and 5 Stage IV-S tumors all had 1 copy of the gene (P less than 0.01). Analysis of progression-free survival in all patients revealed that amplification of N-myc was associated with the worst prognosis (P less than 0.0001); the estimated progression-free survival at 18 months was 70 per cent, 30 per cent, and 5 per cent for patients whose tumors had 1, 3 to 10, or more than 10 N-myc copies, respectively. Of 16 Stage II tumors, 2 with amplification metastasized, whereas only 1 of 14 without amplification did so (P = 0.03). Stage IV tumors with amplification progressed most rapidly: nine months after diagnosis the estimated progression-free survival was 61 per cent, 47 per cent, and 0 per cent in patients whose tumors had 1, 3 to 10, or more than 10 copies, respectively (P less than 0.0001). These results suggest that genomic amplification of N-myc may have a key role in determining the aggressiveness of neuroblastomas.

We investigated the anti-asparaginase antibody (Ab) and asparaginase enzymatic activity in the sera of 1,001 patients (CCG-1961) with high-risk acute lymphoblastic leukemia (HR-ALL). Patients received nine doses of native Escherichia coli asparaginase during induction. Half of rapid early responders (RER) were randomly assigned to standard intensity arms and continued to receive native asparaginase. The other RER patients and all slow early responders received 6 or 10 doses of PEG-asparaginase. Serum samples (n = 3,193) were assayed for determination of asparaginase Ab titers and enzymatic activity. Three hundred ninety of 1,001 patients (39%) had no elevation of Ab among multiple evaluations-that is, were Ab-negative (<1.1 over negative control)-and 611 patients (61%) had an elevated Ab titer (>1.1). Among these 611 patients, 447 had no measurable asparaginase activity during therapy. Patients who were Ab-positive but had no clinical allergies continued to receive E. coli asparaginase, the activity of which declined precipitately. No detectable asparaginase activity was found in 81 of 88 Ab-positive patients shortly after asparaginase injections (94% neutralizing Ab). The Ab-positive patients with clinical allergies subsequently were given Erwinase and achieved substantial activity (0.1-0.4 IU/ml). An interim analysis of 280 patients who were followed for 30 months from induction demonstrated that the Ab-positive titers during interim maintenance-1 and in delayed intensification-1 were associated with an increased rate of events. The CCG-1961 treatment schedule was very immunogenic, plausibly due to initially administrated native asparaginase. Anti-asparaginase Ab was associated with undetectable asparaginase activity and may be correlated with adverse outcomes in HR ALL.

Conditioned anxiety in response to recurrent medical procedures poses a significant problem in the adjustment of children with cancer. Though there is evidence that behavioral approaches can play a role in reducing anxiety, research in this area is hampered by the lack of objective measures of situationspecific anxiety. In the present study, an observational behavior rating scale was developed that enabled us to reliably measure anxiety responses to bone marrow aspirations in 115 children with cancer and to differentiate between low-and high-anxious children, as measured by independent nurses' ratings. Anxiety in response to bone marrow aspirations was virtually ubiquitous in this sample, suggesting the need for clinical intervention. No stable pattern of habituation to this procedure was found. A significant relationship was found between age and both quantity and type of anxious behavior, with younger children tending to emit a greater variety of anxious behaviors over a longer period of time than older children. A developmental trend toward behavioral withdrawal and increased muscle tension with advancing age was also found. Females tended to display higher levels of anxiety than did males, across age groups, and to express this with comfort-seeking, as opposed to uncooperative, behaviors. Age by sex interactions were absent. Results are discussed in terms of the need to consider age and sex when designing treatment and research strategies. A behavioral observation methodology appears promising in terms of its use in a medical setting, from both scientific and pragmatic points of view.Conditioned anxiety related to recurrent both temporal and sensory stimuli (sounds, diagnostic and treatment procedures for sights, and smells), and other stimulus pediatric cancer is a major source of distress discriminants. in children with malignant disease (Katz, Behavioral approaches toward the in press; Zeltzer, Kellerman, Ellenberg, amelioration of acute pain and anxiety in Dash, & Rigler, in press). Such anxiety is children with cancer have included hypnosis often anticipatory (occurring prior to the (Dash, in press; Gardner, 1976; La Baw, administration of medical procedures) and Holton, Lewell, & Eccles, 1975), promanifests itself in a variety of symptoms: cedural preparation (McCue, in press), and nausea and vomiting, anorexia, insomnia, parental relaxation training, along with nightmares, withdrawal, and depression, operant reinforcement of appropriate Though the medical procedures themselves, behavior (Kellerman, 1979). Evaluation of comprised of bone marrow aspirations, the efficacy of such treatment is hampered, lumbar punctures, intravenous and intra-however, by a lack of valid, reliable measmuscular injections of chemotherapeutic urement techniques. agents, are the primary stimuli that evokeIn a recent study, Glennon and Weisz anxiety, substantial stimulus generalization (1978) reviewed the various approaches that occurs, so that children may exhibit anxiety have been used to measure anxiety in young in response ...

Obesity at diagnosis independently predicts likelihood of relapse and cure in preteenagers and adolescents with ALL.