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

Leuk Res. 2008 Dec;32(12):1849-56. doi: 10.1016/j.leukres.2008.05.014. Epub 2008 Jun 27.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alemtuzumab
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • B-Lymphocytes / immunology
  • Cell Survival / drug effects
  • Complement C3b / analysis
  • Drug Resistance, Neoplasm
  • Humans
  • In Vitro Techniques
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Neoplasm Staging
  • Rituximab


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm
  • Antineoplastic Agents
  • Alemtuzumab
  • Rituximab
  • Complement C3b