Imatinib as a single agent at a dose of 440 mg/m(2)/day demonstrated little or no activity as a single agent in children with relapsed or refractory Ewing sarcoma, osteosarcoma, neuroblastoma, or desmoplastic small round cell tumors.

Pseudomonas aeruginosa and Pseudomonas cepacia are catalase-producing bacteria, but only P. cepacia causes infections in patients with chronic granulomatous disease (CGD). The in vitro killing of P. aeruginosa and P. cepacia by polymorphonuclear leukocytes (PMNL) from patients with CGD and from healthy adults was assessed. Of 6 patients with CGD who developed severe infections with P. cepacia, 4 died. PMNL from the 2 survivors and 6 other patients with CGD killed P. aeruginosa strains efficiently and P. cepacia strains poorly. PMNL from 2 patients with autosomal recessive CGD and from 2 carriers for X-linked CGD killed P. cepacia intermediately between normal controls and patients with X-linked CGD. When superoxide anion and hydrogen peroxide were scavenged with superoxide dismutase and catalase, normal PMNL killed P. aeruginosa but not P. cepacia. Thus, P. cepacia, but not P. aeruginosa, is a pathogen in patients with CGD, because it resists neutrophil-mediated nonoxidative bactericidal effects.

Elevated transaminases are common at initial presentation of ALL and are likely due to hepatic injury from leukemic infiltrates. Conjugated hyperbilirubinemia at presentation may require treatment modification and dose reduction. A short course of steroids prior to initiation of induction chemotherapy appears to result in rapid resolution of the hyperbilirubinemia with subsequent ability to provide full dosing of induction chemotherapy.

Current imatinib dosing guidelines in pediatrics is based on the achievement of exposures consistent with doses known to be safe and efficacious in adults. Dose adjustments in children are guided empirically by the observance of drug-related toxicities. While, the pharmacokinetics of imatinib and its active metabolite, CGP 74588 in children are consistent with prior knowledge in adults, the model will form the basis to support the design of future trials, particularly with a view to managing toxicities and exploring dosing in this population.