title: Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab.
abstract: The mechanism of cytotoxicity of alemtuzumab and rituximab in chronic lymphocytic leukemia (CLL) is not well understood. We obtained fresh CLL cells from early-intermediate stage high-risk patients just prior to treatment with alemtuzumab and rituximab to study mechanisms of action and resistance. Alemtuzumab had minimal direct cytotoxicity but caused significant complement dependent cytotoxicity (CDC) although a subpopulation of CLL cells had intrinsic resistance. Rituximab had no direct cytotoxicity and caused minimal CDC in cells from most patients. These data suggest that CDC has a therapeutic role in patients treated with alemtuzumab and that measures to decrease resistance to CDC could increase efficacy.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. zent.clive@mayo.edu
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Charla R
authors.initials: CR
authors.lastname: Secreto
authors.forename: Betsy R
authors.initials: BR
authors.lastname: LaPlant
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Bone
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Renee C
authors.initials: RC
authors.lastname: Tschumper
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D003179:Complement C3b / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D009367:Neoplasm Staging; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D000069283:Rituximab; D003179:Complement C3b