Thymus transplantation for complete DiGeorge syndrome: European experience

Abstract

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 × 10⁶/L (range, 11-440 × 10⁶/L) and 200 × 10⁶/L (range, 5-310 × 10⁶/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10⁶ T cells (range, 320-8,807/10⁶ T cells) and 4,184/10⁶ T cells (range, 1,582-24,596/10⁶ 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.

Keywords: DiGeorge syndrome; athymia; thymus transplantation.