Thymus Transplantation in DiGeorge Syndrome #668

This is an interventional treatment trial for DiGeorge Syndrome focused on measuring Thymus Transplantation, DiGeorge Syndrome, Athymia, Low T cell numbers, Immunoreconstitution, Primary immunodeficiency, DiGeorge Anomaly, Complete DiGeorge, Typical DiGeorge, Cultured Thymus Tissue Implantation (CTTI) Read More

Inclusion Criteria:

• The subject's parent(s) signed the ICF.

• For a diagnosis of DiGeorge Syndrome (DGS), the subject had one of the following:

  • Heart defect
  • Hypoparathyroidism
  • 22q11 hemizygosity
  • 10p13 hemizygosity
  • Coloboma, heart defect, choanal atresia, growth and development retardation, genital hypoplasia, ear anomalies/ deafness CHARGE association mutation (CHD7 deletion);
  • PHA proliferative responses less than 20-fold above background.
• Subjects with typical Complete DiGeorge Anomaly (cDGA) had to have one of the following on 2 separate occasions:

• Circulating CD3+ T cells by flow cytometry < 50/mm3 or PHA < 20-fold over background

  • If CD3+ were > 50/mm3, then CD45RA+ (cluster of differentiation 45RA) CD62L+ had to be < 50/mm3
  • Or T cell receptor rearrangement excision circles (TRECs) by PCR had to be < 100 per 100,000 CD3+ cells.

• Subjects with atypical cDGA had to have both of the following with 2 studies each:

  • Circulating CD3+ T cells by flow cytometry > 500/mm3 and CD45RA+ CD62L+ CD3+ T cells < 50/mm3 and TRECs less than 100 per 100,000 CD3+ cells.
  • T cell proliferative response to PHA more than 20-fold over background. Circulating CD3+ T cells by flow cytometry > 500/mm3 and CD45RA+ CD62L+ CD3+ T cells < 50/mm3 and TRECs less than 100 per 100,000 CD3+ cells.
  • T cell proliferative response to PHA more than 20-fold over background. While T cell response to PHA might have been seen, eligible subjects were to have no T cell proliferative response to antigens (less than 20-fold response) and were to have serious clinical problems related to immunodeficiency, such as opportunistic infection or failure to thrive.

Exclusion Criteria:

• Subjects on ventilators, with tracheostomies, with cytomegalovirus (CMV) infections, or requiring ongoing steroids could still be enrolled, but their data were to be analyzed separately
• Subjects who had heart surgery < 4 weeks prior to transplant
• Heart surgery anticipated within 3 months of the proposed time of transplantation
• Ongoing parenteral steroid therapy between enrollment and transplantation
• Present or past lymphadenopathy
• Rash associated with T cell infiltration of the dermis and epidermis
• Rejection by the surgeon or anesthesiologist as surgical candidates
• Lack of sufficient muscle tissue to accept a transplant of 4 g/m2 body surface area (BSA) of the recipient
• Prior attempts at immune reconstitution, such as bone marrow transplantation or previous thymus transplantation
• Human immunodeficiency virus (HIV) infection