2021 ESMED General Assembly - Results of 105 patients, most with athymia, who received cultured thymus tissue implants (CTTI)

Results of 105 patients, most with athymia, who received cultured thymus tissue implants (CTTI) By Dr. Mary Markert, Duke University Medical Center Abstract: Background: One hundred and three infants with congenital athymia and 2 with severe combined immune deficiency (SCID) have been treated with cultured thymus tissue implantation (CTTRRI) over the past 27 years at a single center. Objectives: Objectives of the study were to assess outcomes including survival, T cell numbers and function, adverse events, and infections. Methods: All patients were enrolled under one of 10 IRB approved protocols. Eligibility was based on naïve T cells lower than 50/mm3 in both typical (no rash) and atypical (rash and lymphadenopathy) groups. A statistical plan was submitted to the Food and Drug Administration (FDA) to be used for all patients regardless of the protocol they were enrolled in. Ten patients who did not meet criteria for CTTI were enrolled in an expanded access protocol and were evaluated separately. Results: The efficacy analysis set (EAS) of 95 patients shows Kaplan-Meier estimated survival rates at year 1 and year 2 post-implantation of 77% and 76% respectively. The median follow-up time for the EAS is 7.6 years and ranged from 0 to 25.5 years. The median CD3 T cell counts remained below the 10th percentile for age. Despite the low CD3 counts, patients, after developing naïve T cells were able to clear disseminated infections such as mycobacteria and parainfluenza III virus. The proliferative response to phytohemagglutinin was normal. In the first year of life there were many adverse events such as fever and line infections. Infections were responsible for 12 deaths. Of the 10 additional patients in the full analysis set, there were 3 deaths yielding a survival similar to that of the EAS. Conclusion: The use of CTTI in athymic infants led to an excellent survival based on the Kaplan Meier Curve of the EAS analysis set. Of 95 patients, there are 70 survivors whose median age is 12.7 years post CTTI. All deaths related to poor immunity occurred in the first 2 years post CTTI. The development of T cell immunity enabled the patients to fight off infection. In summary CTTI is a life-saving investigational therapy for congenital athymia. More details can be found at European Society of Medicine website For more see Facebook of ESMED General Assembly and Youtube of European Society of Medicine

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