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Ann Thorac Surg 2004;77:1734-1739
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

Mycophenolic mofetil reduces the HLA antibody response of children to valved allograft implantation

^a Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah, USA
^b Department of Pathology, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah, USA
^c Department of Surgery, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah, USA

Accepted for publication October 8, 2003.

^* Address reprint requests to Dr Shaddy, Department of Cardiology, Suite 1500, Primary Children's Medical Center, 100 North Medical Dr, Salt Lake City, UT 84113, USA
e-mail: robert.shaddy{at}ihc.com

BACKGROUND: Valved allografts induce a brisk, broadly reactive human leukocyte antigen (HLA) antibody response in children after implantation. Mycophenolic mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of both T cells and B cells and has been reported to possibly reduce HLA panel reactive antibody (PRA) in sensitized transplant recipients.

METHODS: The purpose of this study was to determine whether MMF can blunt the HLA antibody response to valved allografts in children. Eight patients completed (of 28 approached) a pilot study to determine the effects of 3 months of twice daily MMF (600 mg/m²/dose) on the HLA antibody response measured before surgery, at 1 month, and at 3 months after implantation. Patients were 7.5 ± 4 yrs old (mean ± standard deviation [SD]), with 5 patients undergoing repair of tetralogy of Fallot, 2 Ross procedures, and 1 aortic valve replacement.

RESULTS: In contrast to historical controls with a virtual 100% HLA class I PRA response to valved allograft implantation, MMF markedly decreased the HLA class I antibody response at 1 and 3 months postimplantation. In 6 cases where the HLA type of the donor was defined, PRA specificity correlated with incompatible antigens on the allograft. One patient withdrew after 2 weeks due to a sinus infection that was successfully treated with oral antibiotics, and 3 patients had a transient adverse effect of postoperative vomiting.

CONCLUSIONS: This study demonstrates the ability to pharmacologically abrogate the HLA class I antibody response to valved allograft implantation in children using MMF.

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