title: Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients.
abstract: 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 Vbeta (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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. marke001@mc.duke.edu
authors.forename: M Louise
authors.initials: ML
authors.lastname: Markert
authors.forename: Marcella
authors.initials: M
authors.lastname: Sarzotti
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Ozaki
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Maria E
authors.initials: ME
authors.lastname: Rhein
authors.forename: Laura P
authors.initials: LP
authors.lastname: Hale
authors.forename: Francoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Alexieff
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Hauser
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Henry E
authors.initials: HE
authors.lastname: Rice
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skinner
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Mahaffey
authors.forename: James
authors.initials: J
authors.lastname: Jaggers
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Stein
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mill
mesh_terms: D002648:Child; D002675:Child, Preschool; D004062:DiGeorge Syndrome / Q000150:complications / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007107:Immune System / Q000254:growth & development; D007109:Immunity; D007223:Infant; D008213:Lymphocyte Activation; D016377:Organ Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D011948:Receptors, Antigen, T-Cell; D012307:Risk Factors; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000637:transplantation*; D016896:Treatment Outcome
chemical_list: D011948:Receptors, Antigen, T-Cell