Factors Affecting Success of Thymus Transplantation for Complete DiGeorge Anomaly

M. L. Markert; B. H. Devlin; I. K. Chinn; E. A. McCarthy; Y. J. Li


American Journal of Transplantation. 2008;8(8):1729-1736. 

In This Article

Abstract and Introduction


Thymus transplantation shows promise for the treatment of athymia in complete DiGeorge anomaly. This report reviews the effects of dose of thymus tissue, ABO compatibility, HLA matching, culture conditions, age of donor and immunosuppression of recipient on immune outcomes at 1 year after transplantation. Forty-nine athymic subjects have been treated with cultured postnatal allogeneic thymus tissue; 36 (73%) survive with only one subject on immunosuppression at 1.5 years. Of 31 surviving subjects more than 1 year after transplantation, 30 (97%) developed naive T cells, T-cell proliferative responses to mitogens and a diverse T-cell receptor beta variable (TCRBV) repertoire. The dose of thymus tissue, HLA matching and use of immunosuppression had nonsignificant effects on these outcome variables. Removal of deoxyguanosine from culture medium and length of culture did not adversely affect outcomes. Use of thymus tissue from donors over 1 month of age, versus under 1 month, resulted in higher total T-cell numbers (p = 0.03). However, this finding must be confirmed in a prospective trial. Although subtle immune effects may yet be associated with some of the factors tested, it is remarkable that consistently good immune outcomes result despite variation in dose, HLA matching and use of immunosuppression.


Thymus transplantation is being developed under an Investigational New Drug (IND) application with the Food and Drug Administration (FDA) for congenital athymia, which occurs most frequently in DiGeorge anomaly. DiGeorge anomaly is characterized by abnormalities in the heart, thymus and parathyroid glands.[1,2,3,4,5,6,7] Complete DiGeorge anomaly is defined by complete absence of the thymus.[8] Athymia is ascertained by studying the peripheral blood using flow cytometry. Infants with athymia demonstrate a lack of peripheral blood naive T cells (recent athymic emigrants), characterized by the coexpression of CD45RA and CD62L.[9] Athymia is a fatal condition; athymic infants usually die by 2 years of age.[8] Thymus transplantation has shown very promising results with 73% survival in a group of 49 consecutive infants.[10]

With time, infants born with complete DiGeorge anomaly may develop a rash and lymphadenopathy[11,12] associated with oligoclonal expansions of 'host' T cells. Infants with the phenotype of complete DiGeorge anomaly associated with rash and lymphadenopathy are described as having 'atypical' complete DiGeorge anomaly. The oligoclonal T cells can be predominantly CD4 single-positive T cells, predominantly CD8 single-positive T cells or double-negative (CD4-CD8-) T cells.[11] Total T-cell numbers can reach markedly elevated levels in the blood (over 50 000/mm3) and can be associated with infiltration of the liver and elevated liver enzymes. These 'atypical' infants need peritransplantation immunosuppression to prevent graft rejection.[13]

This study evaluated the effect of dose of thymus tissue, ABO compatibility, HLA matching, length of culture, use of deoxyguanosine in culture, age of donor and immunosuppression of the recipient on immune outcomes at 1 year.


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