Treatment of vascular rejection with rituximab in cardiac transplantation

Background: Vascular rejection is the B-cell-mediated production of immunoglobulin G (IgG) antibody against the transplanted heart. The currently available treatments for vascular rejection have had limited success, and chronic manifestations of vascular rejection require Ire-transplantation. Rituximab is a monoclonal antibody directed against the CD20 receptor of B-lymphocytes, which is approved for treatment of lymphoma. Methods: Vascular rejection was defined as positive immunofluorescent endomyocardial biopsy staining for IgG and complement, 25% reduction in left ventricular ejection fraction (LVEF) from baseline, and absence of cellular rejection. Over the last 3 years, 8 patients with vascular rejection were treated with intravenous rituximab at a dose of 375 mg/m(2) per week for 4 weeks. Results: All patients had normal LVEF post-transplant (average 58%), but developed left I ventricular dysfunction (average decrease of 43%) associated with endomyocardial biopsy evidence of vascular rejection. Post-treatment, LVEF returned to baseline (average 53%) with complete resolution of immunofluorescent staining by endomyocardial biopsy. No patient suffered significant infection or drug-related complications. Conclusions: Rituximab is beneficial for treatment of vascular rejection. Further study is indicated to verify the safety, efficacy and mechanism of action of rituximab therapy for vascular rejection.