Concurrent cultured thymus tissue implantation and orthotopic heart transplantation: A case report on the first clinical experience
Lillian Kang1, Joseph R. Nellis1, Nicholas D. Andersen1,2, Henry E. Rice1,3, Michael P. Carboni4,5, M Louise Markert5,6, Joseph W. Turek1,2.
1Department of Surgery, Duke University Medical Center, Durham, NC, United States; 2Children’s Pediatric & Congenital Heart Center, Duke University Medical Center, Durham, NC, United States; 3Division of Pediatric General Surgery, Duke University Medical Center, Durham, NC, United States; 4Division of Pediatric Cardiology, Duke University Medical Center, Durham, NC, United States; 5Department of Pediatrics, Duke University Medical Center, Durham, NC, United States; 6Department of Immunology, Duke University Medical Center, Durham, NC, United States
Introduction: Pediatric cardiac transplantation faces many challenges due to the complications of chronic immunosuppression. Many attempts at establishing transplant tolerance have been made, but one showing promise is concurrent cultured thymus tissue implantation (CTTI) and orthotopic heart transplantation (OHT) from the same donor. CTTI has been used safely and successfully to treat over 100 children with DiGeorge’s anomaly, but this has never been attempted in conjunction with OHT to our knowledge.
Methods: The patient is a 7 month old male with a history of double outlet right ventricle, transposition of the great arteries, aortic arch hypoplasia, ventricular septal defect, and hypoplastic mitral valve for which he underwent a tricuspid valvuloplasty, atrial septectomy, aortic arch reconstruction, main pulmonary artery banding, and subtotal thymectomy on day of life five. Tricuspid valve repair was performed at 6 weeks of age. This was complicated by progressive heart failure along with T cell deficiency of unknown etiology. The patient underwent OHT and completion thymectomy at 6 months of age. The patient was induced with rabbit anti-thymocyte globulin at the time of OHT, then every 24 hours for 5 doses. Immunosuppression regimen included methylprednisolone burst (5mg/kg every 8 hours for 6 doses) and taper (0.5mg/kg daily at discharge), mycophenolate (50mg every 12 hours), and tacrolimus (0.25mg every 12 hours, goal trough level of 8ng/mL). With compassionate use FDA approval, donor thymus obtained from the heart donor at the time of OHT was sliced, cultured, and implanted into bilateral quadriceps 13 days after OHT. A cardiac transplant biopsy was conducted on post-OHT day 12. Manual white blood cell counts, lymphocyte enumeration, and immunoglobulin profiles were measured post-CTTI.
Results: The patient tolerated OHT without complication. All inotropes were weaned by post-OHT day 7. Patient had successful tracheostomy collar trials while awake and support from Trilogy Evo portable ventilator while asleep. He was also able to tolerate tube feedings well with consistent weight gain for the past 4 months with an average weight gain of 27 grams/day for the last 3 days of hospitalization. Patient’s endomyocardial biopsy on post-OHT day 12 showed no signs of acute cellular rejection with ISHLT 2004 Grade 0R nor antibody mediated rejection with pAMR 0. On post-OHT day 39, the lymphocyte enumeration showed 142 CD3 T cells and 59 naïve RA+CD62L+CD3+T cells; B cell and NK cell numbers were also normal for age. IgG levels have remained in the normal range since 3 months of age. The patient’s lymphocyte count has been stable with 1.110 x109/L on post-OHT day 18 and 1.540x109/L on post-OHT day 39. The patient was discharged home on post-OHT day 39 without any other complications.
Conclusion: This patient will be followed closely over the next 2 years to assess the safety of this treatment and any adverse events.
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