Cultured thymus tissue implantation for congenital athymia: Surgical site complications and dose-effect analysis.

PURPOSE: Allogeneic processed thymus tissue-agdc (RETHYMIC®) is the only FDA-approved therapy for immune reconstitution in pediatric patients with congenital athymia. Early mortality due to immune dysregulation and overwhelming infections occurs in the majority of untreated children. Our aims were to report local surgical morbidity of the implantation procedure and evaluate the dose- and volume-effect relationship.

METHODS

We analyzed children in prospective, single-arm open-label studies (IRB Pro00104164), undergoing allogeneic cultured thymic tissue implantation (CTTI) in the quadriceps muscle, between 1993 and 2021. Adverse events, CTT (cultured thymus tissue) doses and naïve T-cell reconstitution at 12 months were reviewed to analyze dose- and volume-effect relationships.

RESULTS

107 children underwent CTTI. Nine (8.4%) surgery-related adverse events (Clavien-Dindo grade I or II) were observed: five cases of wound dehiscence, two stitch abscesses, one surgical site bleed and one surgical site edema managed with compression. Ninety-seven children had treatment-naïve congenital athymia, of which 64 had both a dose reported and T-cell flow cytometry performed 12 months post-implantation. The number of T-cells (CD3, CD4, CD8 and naïve CD4) did not correlate with the administered dose (CD3: r = 0.0472, p = 0.7112, CD4: r = 0.2149, p = 0.0882, CD8: r = -0.048, p = 0.7111, naïve CD4: r = 0.0847, p = 0.5504) or volume (CD3: r = 0.01979, p = 0.1728, CD4: r = 0.139, p = 0.3358, CD8: r = 0.0954, p = 0.5143, naïve CD4: r = 0.0097, p = 0.9525).

CONCLUSION

CTTI was associated with a low rate of procedure-site morbidity in an immunocompromised population. Whereas naïve CD4 T-cells are observed 12 months post-implantation, the dose and volume of CTT does not correlate with the magnitude of the T-cell reconstitution.