Care of Children with DiGeorge Before and After Cultured Thymus Tissue Implantation

Stephanie E Gupton, Elizabeth A McCarthy, M Louise Markert, Stephanie E Gupton, Elizabeth A McCarthy, M Louise Markert

Abstract

Background: Children with complete DiGeorge anomaly (cDGA) have congenital athymia plus a myriad of other challenging clinical conditions. The term cDGA encompasses children with congenital athymia secondary to 22q11.2DS, CHARGE syndrome (coloboma, heart defects, choanal atresia, growth or mental retardation, genital abnormalities, and ear abnormalities and/or deafness), and other genetic abnormalities. Some children have no known genetic defects. Since 1993, more than 100 children with congenital athymia have been treated with cultured thymus tissue implantation (CTTI). Naïve T cells develop approximately 6 to 12 months after CTTI. Most of the children had significant comorbidities such as heart disease, hypoparathyroidism, and infections requiring complex clinical care post cultured thymus tissue implantation (CTTI).

Objective: The purpose of this guidance is to assist multidisciplinary teams in caring for children with cDGA both before and after CTTI.

Methods: Thirty-one specialists, in addition to the authors, were asked to share their experience in caring for children with cDGA at Duke University Health System, before and after CTTI. These specialists included physicians, nurses, dentists, therapists, and dieticians.

Results: The goal of a multidisciplinary approach is to have children in the best possible condition for receiving CTTI and provide optimal care post CTTI through development of naïve T cells and beyond. The CTT (cultured thymus tissue) must be protected from high doses of steroids which can damage CTT. Organs must be protected from adverse effects of immunosuppression.

Conclusion: Creating a multidisciplinary team and a detailed plan of care for children with cDGA is important for optimal outcomes.

Keywords: 22q11.2 deletion syndrome; CHARGE syndrome; Complete DiGeorge anomaly; Congenital athymia; Cultured thymus tissue implantation.

Conflict of interest statement

Cultured thymus tissue implantation (CTTI) is an investigational product implanted into patients under an Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Dr. Markert is the “sponsor” of the investigations. Dr. Markert developed the technology for CTTI. Duke has licensed the technology to Enzyvant Therapeutics GmbH. Dr. Markert and Duke have received royalties from Enzyvant. Portions of Dr. Markert’s and her research team’s salaries are being paid by funding from Enzyvant. If the technology is commercially successful in the future, Dr. Markert and Duke may benefit financially. The salary and other items needed to create CTTI are paid at cost by insurance.

There is no conflict of interest to disclose by Gupton and McCarthy.

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