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, Michael R. Mill

Research output: Contribution to journalArticle

92 Citations (Scopus)

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 Vβ (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.

Original languageEnglish (US)
Pages (from-to)1121-1130
Number of pages10
JournalBlood
Volume102
Issue number3
DOIs
StatePublished - Aug 1 2003

Fingerprint

DiGeorge Syndrome
Thymus
T-cells
Thymus Gland
Transplantation
Safety
T-Lymphocytes
Lymphocytes
Flow cytometry
Immune system
Phytohemagglutinins
T-Cell Antigen Receptor
Mitogens
Immunoglobulin E
Assays
Tracheostomy
Alopecia
Cells
Cytomegalovirus Infections
Eosinophilia

ASJC Scopus subject areas

  • Hematology

Cite this

Markert, M. L., Sarzotti, M., Ozaki, D. A., Sempowski, G. D., Rhein, M. E., Hale, L. P., ... Mill, M. R. (2003). Thymus transplantation in complete DiGeorge syndrome: Immunologic and safety evaluations in 12 patients. Blood, 102(3), 1121-1130. https://doi.org/10.1182/blood-2002-08-2545

Thymus transplantation in complete DiGeorge syndrome : Immunologic and safety evaluations in 12 patients. / Markert, M. Louise; Sarzotti, Marcella; Ozaki, Daniel A.; Sempowski, Gregory D.; Rhein, Maria E.; Hale, Laura P.; Le Deist, Francoise; Alexieff, Marilyn J.; Li, Jie; Hauser, Elizabeth R.; Haynes, Barton F.; Rice, Henry E.; Skinner, Michael A.; Mahaffey, Samuel M.; Jaggers, James; Stein, Leonard D.; Mill, Michael R.

In: Blood, Vol. 102, No. 3, 01.08.2003, p. 1121-1130.

Research output: Contribution to journalArticle

Markert, ML, Sarzotti, M, Ozaki, DA, Sempowski, GD, Rhein, ME, Hale, LP, Le Deist, F, Alexieff, MJ, Li, J, Hauser, ER, Haynes, BF, Rice, HE, Skinner, MA, Mahaffey, SM, Jaggers, J, Stein, LD & Mill, MR 2003, 'Thymus transplantation in complete DiGeorge syndrome: Immunologic and safety evaluations in 12 patients', Blood, vol. 102, no. 3, pp. 1121-1130. https://doi.org/10.1182/blood-2002-08-2545
Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP et al. Thymus transplantation in complete DiGeorge syndrome: Immunologic and safety evaluations in 12 patients. Blood. 2003 Aug 1;102(3):1121-1130. https://doi.org/10.1182/blood-2002-08-2545
Markert, M. Louise ; Sarzotti, Marcella ; Ozaki, Daniel A. ; Sempowski, Gregory D. ; Rhein, Maria E. ; Hale, Laura P. ; Le Deist, Francoise ; Alexieff, Marilyn J. ; Li, Jie ; Hauser, Elizabeth R. ; Haynes, Barton F. ; Rice, Henry E. ; Skinner, Michael A. ; Mahaffey, Samuel M. ; Jaggers, James ; Stein, Leonard D. ; Mill, Michael R. / Thymus transplantation in complete DiGeorge syndrome : Immunologic and safety evaluations in 12 patients. In: Blood. 2003 ; Vol. 102, No. 3. pp. 1121-1130.
@article{5ab561e61d504680a96f16e9fb154ab2,
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 Vβ (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.",
author = "Markert, {M. Louise} and Marcella Sarzotti and Ozaki, {Daniel A.} and Sempowski, {Gregory D.} and Rhein, {Maria E.} and Hale, {Laura P.} and {Le Deist}, Francoise and Alexieff, {Marilyn J.} and Jie Li and Hauser, {Elizabeth R.} and Haynes, {Barton F.} and Rice, {Henry E.} and Skinner, {Michael A.} and Mahaffey, {Samuel M.} and James Jaggers and Stein, {Leonard D.} and Mill, {Michael R.}",
year = "2003",
month = "8",
day = "1",
doi = "10.1182/blood-2002-08-2545",
language = "English (US)",
volume = "102",
pages = "1121--1130",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Thymus transplantation in complete DiGeorge syndrome

T2 - Immunologic and safety evaluations in 12 patients

AU - Markert, M. Louise

AU - Sarzotti, Marcella

AU - Ozaki, Daniel A.

AU - Sempowski, Gregory D.

AU - Rhein, Maria E.

AU - Hale, Laura P.

AU - Le Deist, Francoise

AU - Alexieff, Marilyn J.

AU - Li, Jie

AU - Hauser, Elizabeth R.

AU - Haynes, Barton F.

AU - Rice, Henry E.

AU - Skinner, Michael A.

AU - Mahaffey, Samuel M.

AU - Jaggers, James

AU - Stein, Leonard D.

AU - Mill, Michael R.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - 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 Vβ (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.

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 Vβ (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.

UR - http://www.scopus.com/inward/record.url?scp=0041743085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041743085&partnerID=8YFLogxK

U2 - 10.1182/blood-2002-08-2545

DO - 10.1182/blood-2002-08-2545

M3 - Article

C2 - 12702512

AN - SCOPUS:0041743085

VL - 102

SP - 1121

EP - 1130

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -