Thymus Transplantation in DiGeorge Syndrome #668

There is no safe and effective treatment for DiGeorge syndrome and most patients die by the
age of two. Complete DiGeorge syndrome is characterized by very low T cell or very low naïve
T cell numbers. In this study, typical complete DiGeorge syndrome subjects received human
postnatal cultured thymus tissue transplants. Thymus tissue that would otherwise be discarded
was transplanted into complete DiGeorge subjects in the operating room. At the time of
transplantation, a skin biopsy may have been obtained to look for any preexisting T cells.
After transplantation, subjects were followed by routine research immune evaluations, using
blood samples obtained approximately every 2-4 weeks. At approximately 2-3 months
post-transplantation subjects underwent an open biopsy of the allograft. The biopsy was done
under general anesthesia in the operating room. At the time of the graft biopsy, another skin
biopsy was obtained to look for clonal populations of T cells.

The protocol aims include: assessing thymopoiesis in the allograft biopsy; assessing
immunoreconstitution of complete DiGeorge syndrome subjects after postnatal allogeneic thymus
transplantation; assessing minimally invasive methods of assessing thymopoiesis (flow
cytometry and polymerase chain reaction (PCR); assessing pre-transplant T cells which do not
proliferate in response to mitogens (focusing on NK-T cells); and, assessing thymus
transplantation safety and toxicity.

Inclusion Criteria:

- Diagnosis of complete DiGeorge syndrome which is either: T cells with < 50/mm3 with
naive phenotype; or < 5% CD3 + T cells with naive T cell phenotype.

- Diagnosis of typical DiGeorge syndrome phenotype: < 50 T cells/cumm and very low
proliferative responses to mitogens (e.g. < 20 fold response to mitogen
phytohemagglutinin).

- Proliferative response to PHA < 20 fold above background or < 5000 counts per
minute(cpm), whichever is higher.

{Note: Subjects with PHA responses 20 fold or more over background or > 5,000 cpm,
whichever is higher, may be enrolled in another thymus transplant protocol.}

- Must have heart disease; hypocalcemia requiring replacement; 22q11 or 10p13
hemizygosity; CHARGE association; or must be child of diabetic mother and have
abnormal ears.

Exclusion Criteria:

- Those who do not meet inclusion criteria

- Atypical DiGeorge syndrome phenotype

- Rash indicating atypical DiGeorge syndrome phenotype.

Transplant Exclusion:

- Heart surgery <4 weeks pre-tx date

- Heart surgery anticipated w/in 3 months of proposed tx

- Rejection by surgeon or anesthesiologist as surgical candidates

- Lack of sufficient muscle tissue to accept 0.2 grams/kg transplant