PMID- 12702512 OWN - NLM STAT- MEDLINE DCOM- 20030922 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 102 IP - 3 DP - 2003 Aug 1 TI - Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. PG - 1121-30 AB - 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. FAU - Markert, M Louise AU - Markert ML AD - Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. marke001@mc.duke.edu FAU - Sarzotti, Marcella AU - Sarzotti M FAU - Ozaki, Daniel A AU - Ozaki DA FAU - Sempowski, Gregory D AU - Sempowski GD FAU - Rhein, Maria E AU - Rhein ME FAU - Hale, Laura P AU - Hale LP FAU - Le Deist, Francoise AU - Le Deist F FAU - Alexieff, Marilyn J AU - Alexieff MJ FAU - Li, Jie AU - Li J FAU - Hauser, Elizabeth R AU - Hauser ER FAU - Haynes, Barton F AU - Haynes BF FAU - Rice, Henry E AU - Rice HE FAU - Skinner, Michael A AU - Skinner MA FAU - Mahaffey, Samuel M AU - Mahaffey SM FAU - Jaggers, James AU - Jaggers J FAU - Stein, Leonard D AU - Stein LD FAU - Mill, Michael R AU - Mill MR LA - eng GR - M03-RR30/RR/NCRR NIH HHS/United States GR - R01-AI47040/AI/NIAID NIH HHS/United States PT - Clinical Trial PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030417 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Child MH - Child, Preschool MH - DiGeorge Syndrome/complications/mortality/*therapy MH - Humans MH - Immune System/growth & development MH - Immunity MH - Infant MH - Lymphocyte Activation MH - Organ Transplantation/adverse effects/*methods/mortality MH - Receptors, Antigen, T-Cell MH - Risk Factors MH - T-Lymphocytes/cytology MH - Thymus Gland/*transplantation MH - Treatment Outcome EDAT- 2003/04/19 05:00 MHDA- 2003/09/23 05:00 CRDT- 2003/04/19 05:00 PHST- 2003/04/19 05:00 [pubmed] PHST- 2003/09/23 05:00 [medline] PHST- 2003/04/19 05:00 [entrez] AID - S0006-4971(20)50600-9 [pii] AID - 10.1182/blood-2002-08-2545 [doi] PST - ppublish SO - Blood. 2003 Aug 1;102(3):1121-30. doi: 10.1182/blood-2002-08-2545. Epub 2003 Apr 17.