Background and Aims

Congenital athymia is most frequently associated with complete DiGeorge Syndrome (cDGS). More than 100 cDGS patients have been treated by thymus transplantation (TT)^1,2, including at Great Ormond Street Hospital (GOSH) which offers the only European TT programme, with overall survival of 75-80%. Post-TT, absolute T-cell counts, including naïve T-cells, remain suboptimal. Nevertheless, typically sufficient immune reconstitution is achieved for clearance of pre-existing and acquired infections, as well as discontinuation of antibiotic prophylaxis and immunoglobulin replacement treatment (IgRT). We report long-term outcomes post-TT, including long-term quality of T-cell immunity, which have not previously been described in detail.

Methods

We analysed clinical and laboratory outcomes for cDGS patients with more than 3 years follow-up post-TT.

Results

24 cDGS patients treated between 2009-2018 were included, with a median follow up time of 6.7 years to date (3.4-13.1). No late deaths occurred. At last follow-up, median T-cell counts (/μL) were: CD3⁺ 720, CD4⁺ 500, naïve CD4⁺ 110, CD4⁺ recent thymic emigrants 92, CD8⁺ 180, naïve CD8⁺ 60. Diverse T-cell receptor repertoires persist over time. 19 patients successfully discontinued IgRT and started/completed immunisations. Chronic autoimmunity is common post-TT, with 12 patients suffering autoimmune thyroiditis and 1 autoimmune haemolytic anaemia (AIHA). 2 patients remain on long-term immunomodulatory treatments for either AIHA or inflammatory disease. All bar one patients >5 years of age attend school.

Conclusions

After successful TT in cDGS, satisfactory T-cell immunity is maintained for at least several years facilitating an improved quality of life.

References: ¹Markert et al 2022; ²Davies et al 2017.