Complement activation in circulation and central nervous system after rituximab (anti-CD20) treatment of B-cell lymphoma

Leuk Lymphoma. 2001 Aug;42(4):731-8. doi: 10.3109/10428190109099335.


Rituximab (IDEC-C2B8, Mabthera, Rituxan), a chimeric monoclonal antibody against the B-cell specific CD20-antigen, has been demonstrated to be effective in the treatment of non-Hodgkin's B-cell lymphoma (B-NHL). Previous in vitro studies have shown that direct complement-dependent cytotoxicity (CDC), ADCC and apoptosis are important in the rituximab-induced killing of lymphoma cells. It is, however, unknown whether rituximab penetrates the blood-brain barrier. Therefore, we studied rituximab levels and complement (C) activation in blood and cerebrospinal fluid (CSF) following intravenous rituximab therapy in a patient with relapsing non-Hodgkin's lymphoma with central nervous system (CNS) involvement. Longitudinal samples from blood and CSF were taken at 13 time-points during the treatment period. The results show that the C cascade becomes activated in blood during the first mAb infusion (C3a-desArg concentration rose from 55 to 138 microg/ml during the first 2 hours). After the first infusion the proportions of lymphocytes positive for the CD19- and CD20-antigens in the peripheral blood were reduced from 41% and 35%, respectively, to a level of 2% (for both). In CSF the rituximab concentration increased after successive infusions, but remained below 0.55 microg/ml (compared to a Cmax of 400 microg/ml in peripheral blood). Although a minor and delayed C activation response was seen in the CSF the treatment did not clear CD20-positive cells away from the CNS. Thus, it appears that an intact blood-brain barrier restricts the entry of rituximab into the CNS. Possible options to circumvent this would be dose escalation or intrathecal rituximab treatment.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Blood Circulation / immunology
  • Blood-Brain Barrier
  • Central Nervous System / immunology
  • Cerebrospinal Fluid / chemistry
  • Cerebrospinal Fluid / cytology
  • Cerebrospinal Fluid / drug effects
  • Complement Activation / drug effects*
  • Complement C3a / analogs & derivatives*
  • Complement C3a / cerebrospinal fluid
  • Complement C3a / drug effects
  • Complement C3a / metabolism
  • Humans
  • Lymphoma, B-Cell / cerebrospinal fluid
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / pathology
  • Male
  • Middle Aged
  • Rituximab


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • complement C3a, des-Arg-(77)-
  • Rituximab
  • Complement C3a