Treatment with Rituximab in Benign and Malignant Hematologic Disorders in Children

Abstract

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 malignancies2. Over 540,000 patients have been treated with rituximab worldwide, primarily for B cell lymphomas3. 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 arthritis4. 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 the safety or efficacy of rituximab in children. The package insert states that rituximab has not been studied in children, however, rituximab has been explored in children for a number of hematologic conditions including autoimmune hemolytic anemia (AIHA), chronic immune thrombocytopenic purpura (ITP), antibodies to factors VIII and IX, post transplant lymphoproliferative disease (PTLD), pre B cell acute lymphoblastic leukemia (ALL), and B cell non Hodgkins lymphoma (NHL). This paper will review the current literature on these uses of rituximab in children including articles and abstracts through July 2006.