Rituximab Therapy and Infection Risk in Pediatric Renal Transplant Patients

Abstract

Objectives: Rituximab is a monoclonal antibody directed against the CD20 molecule on pre-B and mature B cells and is used in transplant recipients for the prevention and treatment of alloantibody-mediated rejection or for the treatment of disease recurrence after transplant. In most patients, rituximab has been safe and well-tolerated, but the long-term adverse effects of rituximab are currently unknown.

Materials and Methods: We retrospectively evaluated 78 pediatric renal transplant recipients for the occurrence of infectious disease. Patients who received rituximab therapy were divided into 2 groups: those who developed an infection and those who did not. The 2 groups were compared for serious infections, hospitalization, graft loss, and death rates.

Results: Eighteen transplant patients received rituximab therapy for various causes. The number of rituximab courses given varied according to the cause and ranged from 1 to 8 courses. The dose at each course was 375 mg/m(2). Median age of all recipients was 16.00 years (min-max:, 5.00-22.00 y), and median follow-up time was 2.00 years (min-max:, 1.00-3.00 y). Serious infections (bacterial sepsis, tuberculosis, Cytomegalovirus infection, varicella-zoster virus infection, Polyomavirus-associated nephropathy, and acute pyelonephritis) were observed in 8 patients who received rituximab therapy. We observed that patients with antibody-mediated rejection had significantly increased infection rate. Patients who had used rituximab combined with antithymocyte globulin and higher rituximab course number and higher pretreatment CD19 and CD20 levels had higher risk of infection (P<.05).

Conclusions: The combined use of rituximab with additional treatments such as antithymocyte glob ulin, intravenous immunoglobulin, and repeated plasma exchange may be associated with high risk of infectious disease. Especially for those patients who required intensive and repetitive treatment, such as antibody-mediated rejection, rituximab treatment should be used with caution. Infection risk should be closely monitored, although mainly in patients who receive T-cell-depleting agents.