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Many patients with chronic lymphocytic leukemia (CLL) develop progressive treatment-resistant disease.Rituximab (RTX), a monoclonal antibody targeting CD20 on B lymphocytes and widely used in other indolent B-cell neoplasms is less efficacious in CLL, possibly because of associated complement deficiencies.Initial in vitro and in vivo observations support the central role of complement in rituximab-mediated loss of CD20+ cells in CLL.