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 re-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/m2 per week for 4 weeks.


RESULTS
All patients had normal LVEF post-transplant (average 58%), but developed left 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.
Garrett
H Edward
HE
Division of Cardiothoracic Surgery, Baptist/UT Heart Transplant Program, University of Tennessee, Memphis, Tennessee 38120, USA. beth@cvsclinic.com
Duvall-Seaman
Denise
D
Helsley
Beth
B
Groshart
Kenneth
K
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy*; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D013318:Stroke Volume / Q000187:drug effects
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007074:Immunoglobulin G; D007155:Immunologic Factors; D000069283:Rituximab