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Rituximab

Rituximab

Rituximab was the first monoclonal antibody to be approved for the treatment of cancer. It is a genetically engineered, chimeric monoclonal antibody directed against the CD20 antigen that is found on the surfaces of normal and malignant B lymphocytes. CD20 plays a role in the activation process for cell cycle initiation and differentiation. The CD20 antigen is expressed on nearly all B-cell non Hodgkin lymphomas but not in other bone marrow cells. Rituximab is effective in the treatment of lymphomas, chronic lymphocytic leukemia, and rheumatoid arthritis.

Mechanism of action: 

The Fab domain of rituximab binds to the CD20 antigen on the B lymphocytes, and its Fc domain recruits immune effector functions, inducing complement and antibodydependent, cell-mediated cytotoxicity of the B cells. The antibody is commonly used with other combinations of anticancer agents, such as cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (CHOP).

Adverse effects: 

Severe adverse reactions have been fatal. It is important to infuse rituximab slowly. Hypotension, bronchospasm, and angioedema may occur. Chills and fever commonly accompany the first infusion (especially in patients with high circulating levels of neoplastic cells), because of rapid activation of complement which results in the release of tumor necrosis factor-α and interleukins. Pretreatment with diphenhydramine, acetaminophen, and corticosteroids can ameliorate these problems. Tumor lysis syndrome has been reported within 24 hours of the first dose of rituximab. This syndrome consists of hyperkalemia, hypocalcemia, hyperuricemia, hyperphosphatasemia (an abnormally high content of alkaline phosphatase in the blood), and acute renal failure that may require dialysis.

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