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 × 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.