Concurrent Cultured Thymus Tissue Implantation And Orthotopic Heart Transplantation: A Case Report On The First Clinical Experience
Lillian Kang, MD, James M. Meza, MD, MSc, Nicholas D. Andersen, MD, Henry E. Rice, MD, Michael P. Carboni, MD, M. Louise Markert, MD, Joseph W. Turek, MD, PhD, MBA.
Duke University Medical Center, Durham, NC, USA.
INTRODUCTION Concurrent cultured thymus tissue implantation (CTTI) and orthotopic heart transplantation (OHT) has been proposed as a pathway to develop transplant tolerance. CTTI has been used safely and successfully to treat DiGeorge's anomaly, but this has never been attempted in conjunction with OHT.
METHODS The recipient is a 5 month-old male with unrepairable complex congenital heart disease. He developed progressive heart failure and was observed to have T cell deficiency of unknown etiology. The patient underwent OHT and completion thymectomy at 6 months of age. The patient was induced with rATG for OHT. Immunosuppression included methylprednisolone burst and taper, mycophenolate, and tacrolimus (trough 8ng/mL). With emergency investigational new drug FDA approval, donor thymus obtained from the heart donor was cultured and implanted 13 days after OHT.
RESULTS The patient tolerated OHT and CTTI without complication. He was discharged home on post-OHT day 39. Endomyocardial biopsy on post-OHT day 83 showed no signs of acute cellular rejection (ISHLT 2004 Grade 0R) nor antibody mediated rejection (pAMR 0). On post-CTTI day 266, he demonstrated full immune reconstitution with lymphocyte enumeration of 1,808 CD3 T cells/mm3 and 708/mm3 na´ve RA+CD62L+CD4+ T cells.
CONCLUSION In the world's first CTTI and OHT co-transplant, we have demonstrated immune reconstitution in the presence of standard heart transplant immunosuppression. This case will allow us to test for the development of tolerance with this approach, as immunosuppression is fully weaned. Prior animal studies in our laboratory have demonstrated successful tolerance with this approach.
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