Study: NCT00579527

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation
Description: For subjects w/ hypoparathyroidism, the subject may receive CTTI and parathyroid transplant. For parathyroid transplant, parental parathyroid donors are screened. Parathyroid is harvested from the parent who shares the most Human Leukocyte Antigens (HLA) alleles with the thymus donor. Parathyroid gland is minced and placed in quadriceps muscle; there is no dose. Parathyroid donors are monitored as outpatients until recipients' discharge. Recipients' calcium and PTH levels are monitored indefinitely. Potential thymus recipient subjects are screened for eligibility. Thymus donor (unrelated donor), and thymus donor's birth mother are screened for safety. CTTI is done under general anesthesia in the operating room. Cultured thymus tissue is implanted into the subject's quadriceps. Two to three months post CTTI, if medically stable, the subject undergoes allograft biopsy. At the time of CTTI and biopsy, a skin biopsy is done. Immunosuppression is weaned as per protocol.

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Blood Draw
Description: Birth mothers of Thymus Recipients are asked to participate in the study and undergo phlebotomy to allow testing of T cell identity in the Complete DiGeorge subjects. If blood is not obtainable then a buccal swab may be done.

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Blood Draw
Description: Birth mothers of Thymus Recipients are asked to participate in the study and undergo phlebotomy to allow testing of T cell identity in the Complete DiGeorge subjects. If blood is not obtainable then a buccal swab may be done.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Rabbit anti-thymocyte globulin
Description: Three doses of 2 mg/kg IV (through a central venous catheter) prior to CTTI. Each dose of Rabbit anti-thymocyte globulin (RATGAM) is given over 12 hours. RATGAM is usually given on days-5, -4, and -3 prior to CTTI or CTTI and parathyroid transplantation. Medications (diphenhydramine, steroids, and acetaminophen) are given with rabbit anti-thymocyte globulin.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Rabbit anti-thymocyte globulin
Description: Three doses of 2 mg/kg IV (through a central venous catheter) prior to CTTI. Each dose of Rabbit anti-thymocyte globulin (RATGAM) is given over 12 hours. RATGAM is usually given on days-5, -4, and -3 prior to CTTI or CTTI and parathyroid transplantation. Medications (diphenhydramine, steroids, and acetaminophen) are given with rabbit anti-thymocyte globulin.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Cyclosporine
Description: In addition to RATGAM, subjects with typical cDGA with PHA responses \>50,000 cpm, or atypical cDGA with PHA response \<75,000cpm (when not on immunosuppression) or \<40,000 cpm to PHA while on immunosuppression, are started on cyclosporine (Csa) as soon as cDGA is diagnosed. Csa is continued with target trough levels of 180 to 220 ng/ml. If subject cannot tolerate Csa, Csa may be changed to tacrolimus (FK506) with target trough level 7 to 10 ng/ml. When trough levels are outside of range, dosing is modified appropriately.~Csa may be given every 8 to 12 hours enterally or IV before and after CTTI. The Csa dose is dependent on T cell numbers and the target Csa trough levels. Csa is weaned as per protocol.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Cyclosporine
Description: In addition to RATGAM, subjects with typical cDGA with PHA responses \>50,000 cpm, or atypical cDGA with PHA response \<75,000cpm (when not on immunosuppression) or \<40,000 cpm to PHA while on immunosuppression, are started on cyclosporine (Csa) as soon as cDGA is diagnosed. Csa is continued with target trough levels of 180 to 220 ng/ml. If subject cannot tolerate Csa, Csa may be changed to tacrolimus (FK506) with target trough level 7 to 10 ng/ml. When trough levels are outside of range, dosing is modified appropriately.~Csa may be given every 8 to 12 hours enterally or IV before and after CTTI. The Csa dose is dependent on T cell numbers and the target Csa trough levels. Csa is weaned as per protocol.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Tacrolimus
Description: If unable to tolerate cyclosporine, then tacrolimus is given. Tacrolimus may be given every 8 to 12 hours enterally or IV before and after the CTTI transplant. Tacrolimus dose is dependent on the T cell numbers and the target tacrolimus trough levels. Tacrolimus is weaned as per protocol.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Tacrolimus
Description: If unable to tolerate cyclosporine, then tacrolimus is given. Tacrolimus may be given every 8 to 12 hours enterally or IV before and after the CTTI transplant. Tacrolimus dose is dependent on the T cell numbers and the target tacrolimus trough levels. Tacrolimus is weaned as per protocol.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Methylprednisolone or Prednisolone
Description: Steroids IV or enterally may be given before and after CTTI or CTTI and parathyroid transplantation. Administration and dosage depends on T cell numbers and symptoms. Pre-transplant steroids may be used when pre-transplant T cells \>4,000cumm. Steroids are weaned as per protocol.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Methylprednisolone or Prednisolone
Description: Steroids IV or enterally may be given before and after CTTI or CTTI and parathyroid transplantation. Administration and dosage depends on T cell numbers and symptoms. Pre-transplant steroids may be used when pre-transplant T cells \>4,000cumm. Steroids are weaned as per protocol.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Daclizumab
Description: In addition, subjects with Atypical DiGeorge with PHA responses \>75,000cpm while on no immunosuppression or PHA responses \>40,000cpm while on immunosuppression, Daclizumab 1 mg/kg single dose IV may be given depending on T cell counts. Administration of Daclizumab depends on T cell numbers and T cell activation. A single dose may be given after the administration of rabbit anti-thymocyte globulin and before CTTI. If Daclizumab is not given before CTTI, and, depending on the T cell numbers and T cell activation, a single dose of Daclizumab may be given 3-5 days after CTTI.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Mycophenolate mofetil
Description: In addition, subjects with Atypical DiGeorge with PHA responses \>75,000cpm while on no immunosuppression or PHA responses \>40,000cpm while on immunosuppression, Mycophenolate mofetil 15 mg/kg/dose every 8 hours IV or enterally may be given depending on T cell counts. Mycophenolate mofetil may be given if the T cell count remains elevated 5 days after CTTI. If MMF is given, the dose is 15 mg/kg IV. MMF may be stopped at 35 days after CTTI or continued for up to six months after CTTI.