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Objective
Optimal strategies for maintenance immunosuppression following humoral rejection are unclear. We present a critical analysis of 9 patients treated with cyclic rituximab.
Design
Retrospective Cohort
Setting
Dartmouth-Hitchcock Medical Center
Patients
Review of renal and pancreatic-renal transplants between 1992 and 2010 revealed 13 cases of biopsy-proven acute/delayed-acute humoral rejection. Eleven patients were managed with rituximab. Two patients lost their grafts during initial treatment of the rejection episode, and nine began treatment with cyclic rituximab. Causes of ESRD were diabetic (4), immune (4), PCKD (2), and congenital (1). Eight grafts were cadaveric. Five were sensitized recipients undergoing re-transplantation.
Interventions
Initial treatment of the rejection episodes included thymoglobulin, plasmapheresis, IVIG, steroid and rituximab. Thereafter patients received a 375 mg / m² BSA dose of rituximab weekly for four weeks at 22-week intervals.
Main Outcome Measures
Graft survival, mean IgG levels, and infectious complications.
Results
The mean time to the humoral rejection episode was 441 days. Four patients have functioning grafts with a mean post-rejection survival of 5 years (range 2-9) and mean serum creatinine of 1.4 (range 1.0 - 1.5). Mean post-rejection survival of the five lost grafts was 2.8 years (range 0-5). Three lost grafts were biopsied during rituximab therapy and none were C4d positive. Mean IgG levels were 784 mg/dL. Seven patients required IVIG. Patients experienced an average of one infectious complication per year of treatment, and there were no deaths from infection. To date all surviving recipients display persistence of their donor specific antibody.
Conclusions
Cyclic rituximab is a safe strategy for maintenance immunosuppression following humoral rejection and provides durable blockade of antibody mediated rejection. Vigilance against acquired hypogammaglobulinemia is required.