Pharmacodynamics of rituximab in kidney allotransplantation

Am J Transplant. 2006 Oct;6(10):2418-28. doi: 10.1111/j.1600-6143.2006.01497.x. Epub 2006 Aug 21.

Abstract

The anti-CD20 antibody rituximab has recently gained interest as a B-cell depleting agent in renal transplantation. However, little is known about the pharmacodynamics of rituximab in renal transplant recipients. We have therefore studied the effect of single-dose rituximab in combination with conventional triple immunosuppressive therapy on the B-cell population in peripheral blood as well as in tissues. A total of 49 renal transplant recipients received single-dose rituximab, as induction therapy (n = 36) or as anti-rejection therapy (n = 13). We counted B cells in peripheral blood and performed immunohistochemical staining on lymph nodes and kidney transplant tissue samples to assess the prevalence of B cells. In all but 6 patients (88%) complete depletion of B cells in peripheral blood was achieved. In adults, 15 months after treatment the CD19+ and CD20+ cell counts were still below 5 cells/muL in the majority of patients (78%). The immunohistochemical staining showed a complete elimination of B cells in kidney tissue and a reduction of B cells in lymph nodes. In conclusion, single-dose rituximab in kidney transplant recipients evokes a long-term elimination of B cells in peripheral blood as well as within the kidney transplant. The effect seems to extend beyond the expected 3-12 months observed in lymphoma patients.

Trial registration: ClinicalTrials.gov NCT00255593.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19 / immunology
  • Antigens, CD20 / immunology
  • B-Lymphocytes / immunology
  • Biopsy
  • Child
  • Flow Cytometry
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / drug therapy*
  • Graft Rejection / immunology
  • Humans
  • Immunologic Factors / pharmacokinetics*
  • Immunologic Factors / therapeutic use
  • Kidney Transplantation / immunology
  • Kidney Transplantation / pathology*
  • Lymph Nodes / pathology
  • Retrospective Studies
  • Rituximab
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19
  • Antigens, CD20
  • Immunologic Factors
  • Rituximab

Associated data

  • ClinicalTrials.gov/NCT00255593