Monoclonal antibodies (mAbs) have had a major impact on the diagnosis and treatment of many disorders. First discovered in the 1980s, the original monoclonal antibodies were composed entirely of mouse protein which resulted in the development of human anti-mouse antibodies (HAMA) preventing repeated use. Advances in antibody engineering resulted in chimeric antibodies, with both human and mouse components, and more recently humanized antibodies comprised of almost all human protein (>90%) 1. The reduction in the mouse components of monoclonal antibodies has allowed for these treatments to be repeated by lessening or eliminating development of human anti-mouse antibodies. Tens of thousands of monoclonal antibodies have been produced but less than 20 have been licensed for use in patients in the United States. Rituximab is a chimeric monoclonal antibody specific for CD20, an antigen expressed on B cells. In 1997, it was the third monoclonal antibody approved by the FDA following OKT3 and abciximab. The efficacy of rituximab for the treatment of non-Hodgkin's B cell lymphoma and its relative lack of toxicity lead to its incorporation in most standard treatment protocols for B cell lymphomas and its use in a wide spectrum of B cell disorders, including autoimmune diseases and other malignancies 2. Over 540,000 patients have been treated with rituximab worldwide, primarily for B cell lymphomas 3. There are only two monoclonal antibodies that have been more widely used, both of which are also chimeric: abciximab, an anti-integrin used in more than one million cardiac patients, and infliximab, an anti-TNF-alpha used in approximately 770,000 patients with Crohn disease and rheumatoid arthritis 4. Although rituximab has been widely used in adults for 10 years, studies in the pediatric population are limited and include primarily case reports, small retrospective and small prospective cohort studies. Specifically, there have been no randomized controlled studies of

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3055 Background: The COG trial ANHL01P1 was undertaken to determine pharmacokinetics (PK) and safety following the addition of rituximab (R) to FAB/LMB 96 chemotherapy in children and adolescents with stage III/IV mature B-NHL and B-ALL±CNS disease. Methods: Patients received R (375mg/m2) on day -2 and 0 of two induction cycles and day 0 of two consolidation cycles. R levels were measured prior to any antibody infusion, during induction cycles (1 hour prior and 30-60 minutes after each R dose) and following consolidation cycles (1, 3, 6 and 9 months after last R dose). R was measured by ELISA with goat anti-rituximab antibody as the capture reagent and goat anti-mouse IgG-conjugated to horseradish peroxidase as the detection reagent. R terminal half-life (t½) was calculated if at least 3 time points after the last dose were measurable in an individual subject. Results: Serum R levels are reported in the Table. Highest peak levels were achieved following the second dose of each induction cycle with sustained troughs and a t½ of 26-29 days. Group C patients tended to have lower R levels than Group B. Patients with LDH ≥2xULN were noted to have lower R levels during induction 1 compared to those with LDH <2xULN. Children (<13 years) exhibited higher peak concentrations, similar trough levels and a shorter t½ than adolescents (≥13 years). None of these differences reached significance after adjusting for multiple comparisons. Conclusions: R can be safely added to FAB chemotherapy with high early R peak/trough levels and a long terminal half-life. The efficacy of R combined with FAB chemotherapy is currently being investigated in an ongoing international intergroup trial. Clinical trial information: NCT00057811. [Table: see text]