Thymus transplantation for complete DiGeorge syndrome: European experience

Davies, E. Graham; Cheung, Melissa; Gilmour, Kimberly; Maimaris, Jesmeen; Curry, Joe; Furmanski, Anna; Sebire, Neil; Halliday, Neil; Mengrelis, Konstantinos; Adams, Stuart; Bernatoniene, Jolanta; Bremner, Ronald; Browning, Michael; Devlin, Blythe; Erichsen, Hans Christian; Gaspar, H. Bobby; Hutchison, Lizzie; Ip, Winnie; Ifversen, Marianne; Leahy, T. Ronan; McCarthy, Elizabeth; Moshous, Despina; Neuling, Kim; Pac, Malgorzata; Papadopol, Alina; Parsley, Kathryn L.; Poliani, Luigi; Ricciardelli, Ida; Sansom, David M.; Voor, Tiia; Worth, Austen; Crompton, Tessa; Markert, M. Louise; Thrasher, Adrian J.

BACKGROUND: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). METHODS: Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. OBJECTIVE: We sought to confirm and extend the results previously obtained in a single center. RESULTS: Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 10(6)/L (range, 11-440 × 10(6)/L) and 200 × 10(6)/L (range, 5-310 × 10(6)/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10(6) T cells (range, 320-8,807/10(6) T cells) and 4,184/10(6) T cells (range, 1,582-24,596/10(6) T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1). CONCLUSIONS: This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors.