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

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.

Congenital Athymia: Unmet Needs and Practical Guidance

“…For example, it is crucial to avoid surgical procedures requiring prolonged anaesthetics in the months following thymus transplantation and to avoid certain medications until thymopoiesis is well established in the thymic graft. 8,30,76 Systemic steroids in particular will have a negative effect on the developing thymus tissue. These are standard treatments in the management of respiratory exacerbations in patients with complex airways problems and for the treatment of autoimmune cytopaenias, in particular autoimmune haemolytic anaemia (AIHA), which can occur after thymus transplantation.…”

“…These are standard treatments in the management of respiratory exacerbations in patients with complex airways problems and for the treatment of autoimmune cytopaenias, in particular autoimmune haemolytic anaemia (AIHA), which can occur after thymus transplantation. 3,8,77 Whenever possible, steroid-sparing strategies should be explored until proof of satisfactory thymic output has been obtained. For patients treated at GOSH, a biopsy procedure at the site of thymus tissue implantation is typically scheduled at approximately 3 months after transplantation in order to evaluate the degree of thymopoiesis in the graft 3,78 as this can help in therapeutic decision-making should complications arise before thymic output can be detected in the peripheral blood.…”

“…The US experience has been well documented with comprehensive guidance for clinicians providing care for children with syndromic congenital athymia. 8 The associated heavy economic burden has also been estimated within the American health system for children receiving supportive care only in the first 3 years of life. 79 A comparable burden has been reported with many rare diseases in which the nature of their complexity and intense need for supportive health-care measures create both direct and indirect economic burden.…”

“…2,3 Congenital athymia is a rare condition and patients often have acute and chronic complex care needs, requiring extraordinary specialist care with close collaboration across several teams and centres. 8 Understanding the natural history of the condition and comprehensively recording outcomes after thymus transplantation, including the QOL reported by the patients and their families, are crucial to improving the long-term health and social care services available to this cohort of patients. Analysis of the clinical outcomes after thymus transplantation demonstrates the ability of patients to live a near normal life from an immunological perspective, yet significant challenges remain in terms of optimising overall outcomes for many patients with congenital athymia (see Table 1).…”

Navigating diagnostic options for inborn errors of immunity in children: a case-based illustration

“…In cDGS, left untreated, athymia typically results in recurrent and persistent infections due to viral, bacterial and fungal pathogens and death by age 2 years. The treatment of choice for cDGS or other forms of congenital athymia is a cultured thymic transplant [8 ▪▪ ,19,20].…”