Thymus Transplantation Safety-Efficacy

Complete DiGeorge anomaly (cDGA) is a congenital disorder characterized by athymia. Without
successful treatment, children remain immunodeficient and usually die by age 2 years. In
complete DiGeorge subjects, thymus transplantation with and without immunosuppression has
resulted in diverse T cell development and good T cell function. The purpose of this expanded
access study is to continue thymus transplantation safety and efficacy research for the
treatment of complete DiGeorge anomaly. Until thymus transplantation is FDA approved as
standard care for complete DiGeorge anomaly, 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.

Eligible subjects undergo thymus transplantation and may undergo an allograft biopsy.
Protocol specified studies continue until approximately one year post-transplantation.

Study participation lasts two years or until thymus recipients are asked to participate in a
long-term follow-up study.

Transplant Inclusion:

- Must have 1 of following: 22q11 or 10p13 hemizygosity; hypocalcemia requiring
replacement; congenital heart disease; or CHARGE syndrome or CHD7 mutation

- Complete DiGeorge: <50 CD3+ T cells/cumm or <50 CD3+ T cells/cumm that are CD62L+
CD45RA+, or <5% of CD3+ cells are CD62L+ CD45RA+

- Atypical DiGeorge subjects must have, or have had, a rash.

Group 1

•Typical cDGA whose T cells have a PHA response < 5,000 cpm and < 20 fold PHA response.

Group 2

•Typical cDGA whose T cells have a PHA response >5,000 cpm and <50,000 cpm and >20 fold PHA
response

Group 3

- Typical cDGA whose T cells have PHA response >50,000 cpm

- Typical cDGA with maternal engraftment

- Atypical cDGA whose T cells have PHA response <40,000 cpm when on immunosuppression or
<75,000 cpm to PHA when not on immunosuppression

- Atypical cDGA with group 3 PHA response & maternal engraftment

Group 4

- Atypical cDGA with PHA responses >75,000cpm while on no immunosuppression or PHA
responses >40,000cpm while on immunosuppression

- Atypical cDGA with maternal engraftment and group 4 PHA response

Transplant Exclusion:

- Heart surgery <4 wks pre-transplantation

- Heart surgery anticipated w/in 3 months after proposed transplantation

- Rejection by surgeon or anesthesiologist as surgical candidate

- Lack of sufficient muscle tissue to accept transplant of 2,000 mm2/m2 body surface
area

- HIV infection

- Prior attempts at immune reconstitution, such as bone marrow transplant or previous
thymus transplant

- CMV on 2 tests for Groups 2, 3, and 4

Biological Mother Inclusion/Exclusion:

• Must be biological mother of thymus recipient