Safety and Efficacy of Thymus Transplantation in Complete DiGeorge Anomaly, IND#9836

Complete DiGeorge anomaly (cDGA) is a congenital disorder characterized by athymia. Without successful treatment, patients with cDGA must remain in reverse isolation to prevent infection and subsequent death. In patients with cDGA, implantation of cultured thymus tissue with and without immunosuppression has resulted in diverse T cell development and good T cell function. Protocol specified studies continue until approximately one year post-implantation. Study participation lasts two years.

Patients with Typical complete DiGeorge Anomaly usually have a) less than 50 naive T cells/mm3 or naive T cells that are less than 5% of T cells and b) a low proliferative responses to mitogens (e.g. < a 20 fold response to the mitogen phytohemagglutinin or a response of fewer than 5,000 cpm). These patients do not have diffuse rashes or lymphadenopathy. Occasional patients with typical complete DiGeorge anomaly have proliferative responses to mitogens. Patients with the typical phenotype can develop an atypical phenotype with time.

Patients with Atypical complete DiGeorge Anomaly meet the criteria for athymia (less than 50/mm3 naive T cells or less than 5% of the T cells having the naive phenotype). Patients with the atypical phenotype have developed rash, lymphadenopathy, and oligoclonal T cells. The T cells may infiltrate the liver resulting in elevated liver transaminases. The oligoclonal T cells developing in patients with DiGeorge anomaly may or may not respond to the mitogen phytohemagglutinin (PHA) in vitro.

The purpose of this expanded access study is to continue cultured thymus tissue safety and efficacy research for the treatment of athymia in patients with cDGA. Until administration of cultured thymus tissue is FDA approved as standard care for cDGA, research study participation is the only means by which a patient may have access to this potentially life-saving procedure.

This protocol includes 4 groups: one for subjects who do not require immunosuppression; and 3 immunosuppression groups for subjects with different T cell function levels to be suppressed adequately.