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MO4.6 Concurrent cultured thymus tissue implantation and orthotopic heart transplantation: a case report on the first clinical experience

Lillian Kang, United States

Duke University Medical Center


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.


[1] Kwun J, Li J, Rouse C, Park JB, Farris AB, Kuchibhatla M, Turek JW, Knechtle SJ, Kirk AD, Markert ML. Cultured thymus tissue implantation promotes donor-specific tolerance to allogeneic heart transplants. JCI Insight. 2020 Jun 4;5(11):e129983. doi: 10.1172/jci.insight.129983. PMID: 32352934; PMCID: PMC7308047.
[2] Markert, Mary Louise (Durham, NC, US). 2019. CULTURED THYMUS TISSUE TRANSPLANTATION PROMOTES DONOR-SPECIFIC TOLERANCE TO ALLOGENEIC SOLID ORGAN TRANSPLANTS. United States. Duke University & Medical Center (Durham, NC, US). 20190262402.
[3] GBD 2017 Congenital Heart Disease Collaborators. Global, regional, and national burden of congenital heart disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Child Adolesc Health. 2020 Mar;4(3):185-200. doi: 10.1016/S2352-4642(19)30402-X. Epub 2020 Jan 21. Erratum in: Lancet Child Adolesc Health. 2020 Feb 7;: PMID: 31978374; PMCID: PMC7645774.
[4] Markert ML, Boeck A, Hale LP, Kloster AL, McLaughlin TM, Batchvarova MN, Douek DC, Koup RA, Kostyu DD, Ward FE, Rice HE, Mahaffey SM, Schiff SE, Buckley RH, Haynes BF. Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med. 1999 Oct 14;341(16):1180-9. doi: 10.1056/NEJM199910143411603. PMID: 10523153.
[5] Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sedlak DA, Sempowski GD, Hale LP, Rice HE, Mahaffey SM, Skinner MA. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood. 2004 Oct 15;104(8):2574-81. doi: 10.1182/blood-2003-08-2984. Epub 2004 Apr 20. PMID: 15100156.
[6] Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15;109(10):4539-47. doi: 10.1182/blood-2006-10-048652. Epub 2007 Feb 6. PMID: 17284531; PMCID: PMC1885498.