Phase 2 clinical trial of intrathecal topotecan in children with refractory leptomeningeal leukemia: a Children's Oncology Group trial (P9962).

PURPOSE: We performed a phase 2 study in children with recurrent or refractory leptomeningeal leukemia to determine the objective response rate after treatment with intrathecal (IT) topotecan. PATIENTS AND METHODS: Patients received age-adjusted IT topotecan (0.4 mg/dose for patients >3 years of age) administered twice weekly (every 3-4 days) for 6 weeks during induction, weekly for 4 weeks during consolidation, and twice monthly for 4 months and then monthly thereafter during maintenance. RESULTS: Twenty-two patients enrolled in the study, of whom 20 were eligible and assessable for toxicity and 16 were assessable for response. Of 16 patients, 6 (38%) had a complete response, 8 (50%) had stable disease, and 2 (13%) had progressive disease. The median event-free survival time (95% CI) was 3.1 (1.6-10.3) months and the median overall survival time (95% CI) was 18.0 (7.3-38.3) months. Eight patients (40%) experienced grade 3 or 4 adverse events. There were no grade 4 neurological events (Table III). Four patients experienced a total of 6 grade 3 neurological events including an olfactory seizure, a headache, transient grade 3 speech impairment, muscle weakness, motor neuropathy, and ataxia. Headache was the most common grade ≤2 neurologic event and two patients developed grade ≤2 arachnoiditis. CONCLUSION: IT administration of topotecan was tolerable on this dose and schedule. The majority of adverse events were mild to moderate, reversible side effects. Complete central nervous system remissions were achieved in a subset of children with recurrent or refractory central nervous system leukemia.

Detection of hypertrophic cardiomyopathy is improved when using advanced rather than strictly conventional 12-lead electrocardiogram.

INTRODUCTION: Twelve-lead electrocardiogram (ECG) is used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of HCM patients do not have distinctly abnormal ECGs, whereas up to 5% to 15% of healthy athletes do. We hypothesized that an approximately 5-minute resting advanced 12-lead ECG test ("A-ECG score") could detect HCM with greater sensitivity than pooled conventional ECG criteria and distinguish healthy athletes from HCM with greater specificity. MATERIALS AND METHODS: Five-minute 12-lead ECGs were obtained from 56 HCM patients, 56 age/sex-matched healthy controls, and 69 younger endurance-trained athletes. Electrocardiograms were analyzed using recently suggested pooled conventional ECG criteria and also A-ECG scoring techniques that considered results from multiple advanced and conventional ECG parameters. RESULTS: Compared with pooled criteria from the strictly conventional ECG, an A-ECG logistic score incorporating results from just 3 advanced ECG parameters (spatial QRS-T angle, unexplained portion of QT variability, and T-wave principal component analysis ratio) increased the sensitivity of ECG for identifying HCM from 89% (78%-96%) to 98% (89%-100%; P = .025), while increasing specificity from 90% (83%-94%) to 95% (92%-99%; P = .020). CONCLUSIONS: Resting 12-lead A-ECG scores that are simultaneously more sensitive than pooled conventional ECG criteria for detecting HCM and more specific for distinguishing healthy athletes and other healthy controls from HCM can be constructed. Pending further prospective validation, such scores may lead to improved ECG-based screening for HCM.