Abstract
Rituximab, an anti CD20 monoclonal antibody, is widely used in the treatment of B-cell malignancies in adults and increasingly in pediatric patients. By depleting B-cells, rituximab interferes with humoral immunity. This review provides a comprehensive overview of immune reconstitution and infectious complications after rituximab treatment in children and adolescents. Immune reconstitution starts usually after six months with recovery to normal between nine to twelve months. Extended rituximab treatment results in a prolonged recovery of B-cells without an increase of clinically relevant infections. The kinetic of B-cell recovery is influenced by the concomitant chemotherapy and the underlying disease. Intensive B-NHL treatment such as high-dose chemotherapy followed by rituximab bears a risk for prolonged hypogammaglobulinemia. Overall transient alteration of immune reconstitution and infections after rituximab treatment are acceptable for children and adolescent without significant differences compared to adults. However, age related disparities in the kinetic of immune reconstitution and the definitive role of rituximab in the treatment for children and adolescents with B-cell malignancies need to be evaluated in prospective controlled clinical trials.
Highlights
Rituximab is a chimeric human-mouse monoclonal antibody that reacts with the CD20 antigen expressed on normal and neoplastic B lymphocytes
For the Non Hodgkin lymphoma (NHL)-BFM patients, hypogammaglobulinemia about 12 months after start of therapy was reported for about 50% of the patients without significant differences between patients receiving chemotherapy alone or chemotherapy combined with one dose of rituximab
The observation of altered immunoglobulin levels in pediatric patients might be influenced by host factors as for example the underlying disease and the cytokine release status on the one hand, and on the chemotherapeutic agents and rituximab administration schedule on the other hand. To further analyze this observation we searched for publications reporting the kinetic of immune reconstitution in children and adolescents who received even more intense treatment like myeloablative high dose chemotherapy and stem cell transplantation
Summary
Rituximab is a chimeric human-mouse monoclonal antibody that reacts with the CD20 antigen expressed on normal and neoplastic B lymphocytes. Different mechanisms of action for rituximab include complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and direct induction of apoptosis [1]. Binding of rituximab to CD20 causes rapid depletion of B-cells [5,6] This is followed by a new ontogeny repopulation of the B cell pool characterized first by the appearance of immature cells (CD38, CD10, CD24), later naïve B cells and CD27 memory B cell. In the treatment of B-cell malignancies in adults, rituximab is effective and well established. Details of the reconstitution of the B cell pool and the question whether rituximab treatment results in more severe immunological late effects when administered to young patients with a more immature immune system are addressed in the current review
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