Basiliximab (Simulect) for the treatment of steroid-resistant rejection in pediatric liver transpland recipients: a preliminary experience.
BACKGROUND
The role of interleukin-2 receptor antibodies as rescue therapy in steroid-resistant rejection (SRR) has not been studied. We evaluated the safety and efficacy of an interleukin-2 receptor antibody, basiliximab (Simulect, Novartis, East Hanover, NJ), in treating SRR in pediatric liver transplant recipients.


METHODS
This was a prospective study of seven pediatric liver transplant recipients with biopsy-proven SRR who would have otherwise received OKT3 or antithymocyte globulin. The primary immunosuppression consisted of cyclosporine (Neoral, Novartis), azathioprine, and prednisolone in four patients and tacrolimus and prednisolone in three patients who had undergone retransplantation for chronic rejection (n=2) and hyperacute rejection (n=1). Four patients had received two cycles of high-dose steroids, and three patients had received a single cycle; all had been converted to tacrolimus, followed by the addition of mycophenolate mofetil.


RESULTS
The median time from transplant to SRR was 30 days (range, 8 days-23 months). Five children received two doses of basiliximab (10 mg, 3-7 days apart), and two children received a single dose. Aspartate aminotransferase levels normalized in three children 12, 21, and 30 days after basiliximab treatment. Aspartate aminotransferase levels decreased without normalizing in two children, but there was no further evidence of cellular rejection on repeat biopsies. All five children are rejection-free with a median follow-up of 22 months (range, 5-32 months). Biochemical abnormalities persisted in the remaining two children, and both developed chronic rejection. There were no immediate side effects associated with basiliximab. Two patients were treated empirically for possible cytomegalovirus infection 21 and 57 days after basiliximab treatment, with no evidence of cytomegalovirus disease.


CONCLUSIONS
Five of seven pediatric liver transplant recipients with SRR experienced successful outcomes with basiliximab treatment without major side effects, indicating that it is a safe alternative to OKT3 and other antilymphocyte antibodies.
Aw
M M
MM
Department of Pediatrics, National University of Singapore, Children's Medical Institute, National University Hospital, Singapore.
Taylor
R M
RM
Verma
A
A
Parke
A
A
Baker
A J
AJ
Hadzic
D
D
Muiesan
P
P
Rela
M
M
Heaton
N D
ND
Mieli-Vergani
G
G
Dhawan
A
A
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000077552:Basiliximab; D001663:Bilirubin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007223:Infant; D016031:Liver Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010865:Pilot Projects; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology; D011993:Recombinant Fusion Proteins; D016559:Tacrolimus / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D009173:Mycophenolic Acid; D001663:Bilirubin; D016559:Tacrolimus