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Prepublished online as a Blood First Edition Paper on April 17, 2003; DOI 10.1182/blood-2002-08-2545.
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Blood, 1 August 2003, Vol. 102, No. 3, pp. 1121-1130
TRANSPLANTATION
Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients
M. Louise Markert,
Marcella Sarzotti,
Daniel A. Ozaki,
Gregory D. Sempowski,
Maria E. Rhein,
Laura P. Hale,
Francoise Le Deist,
Marilyn J. Alexieff,
Jie Li,
Elizabeth R. Hauser,
Barton F. Haynes,
Henry E. Rice,
Michael A. Skinner,
Samuel M. Mahaffey,
James Jaggers,
Leonard D. Stein, and
Michael R. Mill
From the Departments of Pediatrics, Immunology, Medicine, Pathology, and Surgery, and the Human Vaccine Institute, Duke University Medical Center, Durham, NC; Departments of Pediatrics and Surgery, the University of North Carolina, Chapel Hill, NC; and Laboratoire d'Immunologie Pédiatrique, Hospital Necker Enfants Malades, Paris, France
Complete DiGeorge syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of thymus transplantation were evaluated in 12 infants with complete DiGeorge syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor V (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge syndrome.
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