BACKGROUND: Therapeutic options for DiGeorge syndrome (DGS) with profound T-cell deficiency are very limited. Thymic transplantation has shown promising results but is not easily available. Hematopoietic cell transplantation (HCT) has been successful in restoring immune competence in the short term. OBJECTIVE: Present the long-term follow-up of 2 patients with complete DGS who received bone marrow transplants in the neonatal period from HLA-matched siblings, and perform a multicenter survey to document the status of other patients with DGS who have undergone HCT. METHODS: Immune function assessment by immunophenotyping, lymphocyte proliferation, T-cell receptor excision circles, single nucleotide polymorphism mapping arrays, spectratyping, cytogenetics, and fluorescence in situ hybridization were used. RESULTS: Among reported patients with DGS receiving HCT, survival is greater than 75%. Our patients are in their 20s and in good health. Their hematopoietic compartment shows continuous engraftment with mixed chimerism, normal T-cell function, and humoral immunity. Circulating T cells exhibit a memory phenotype with a restricted repertoire and are devoid of T-cell receptor excision circles. CONCLUSION: These features suggest that T-cell reconstitution has occurred predominantly through expansion of the donors' mature T-cell pool. Although restricted, their immune systems are capable of providing substantial protection to infection and respond to vaccines. We conclude that bone marrow transplant achieves long-lived reconstitution of immune function in complete DGS and is a good alternative to thymic transplantation in patients with a suitable donor. CLINICAL IMPLICATIONS: Bone marrow transplant in complete DGS using an HLA-matched sibling donor provides long-lasting immunity and is a suitable and more available alternative to thymic transplantation.
BACKGROUND: Therapeutic options for DiGeorge syndrome (DGS) with profound T-cell deficiency are very limited. Thymic transplantation has shown promising results but is not easily available. Hematopoietic cell transplantation (HCT) has been successful in restoring immune competence in the short term. OBJECTIVE: Present the long-term follow-up of 2 patients with complete DGS who received bone marrow transplants in the neonatal period from HLA-matched siblings, and perform a multicenter survey to document the status of other patients with DGS who have undergone HCT. METHODS: Immune function assessment by immunophenotyping, lymphocyte proliferation, T-cell receptor excision circles, single nucleotide polymorphism mapping arrays, spectratyping, cytogenetics, and fluorescence in situ hybridization were used. RESULTS: Among reported patients with DGS receiving HCT, survival is greater than 75%. Our patients are in their 20s and in good health. Their hematopoietic compartment shows continuous engraftment with mixed chimerism, normal T-cell function, and humoral immunity. Circulating T cells exhibit a memory phenotype with a restricted repertoire and are devoid of T-cell receptor excision circles. CONCLUSION: These features suggest that T-cell reconstitution has occurred predominantly through expansion of the donors' mature T-cell pool. Although restricted, their immune systems are capable of providing substantial protection to infection and respond to vaccines. We conclude that bone marrow transplant achieves long-lived reconstitution of immune function in complete DGS and is a good alternative to thymic transplantation in patients with a suitable donor. CLINICAL IMPLICATIONS: Bone marrow transplant in complete DGS using an HLA-matched sibling donor provides long-lasting immunity and is a suitable and more available alternative to thymic transplantation.
Authors: Ales Janda; Petr Sedlacek; Manfred Hönig; Wilhelm Friedrich; Martin Champagne; Tadashi Matsumoto; Alain Fischer; Benedicte Neven; Audrey Contet; Danielle Bensoussan; Pierre Bordigoni; David Loeb; William Savage; Nada Jabado; Francisco A Bonilla; Mary A Slatter; E Graham Davies; Andrew R Gennery Journal: Blood Date: 2010-06-07 Impact factor: 22.113
Authors: Suk See De Ravin; Edward W Cowen; Kol A Zarember; Narda L Whiting-Theobald; Douglas B Kuhns; Netanya G Sandler; Daniel C Douek; Stefania Pittaluga; Pietro L Poliani; Yu Nee Lee; Luigi D Notarangelo; Lei Wang; Frederick W Alt; Elizabeth M Kang; Joshua D Milner; Julie E Niemela; Mary Fontana-Penn; Sara H Sinal; Harry L Malech Journal: Blood Date: 2010-05-20 Impact factor: 22.113
Authors: David Buchbinder; Jolan E Walter; Manish J Butte; Wan-Yin Chan; Maria Chitty Lopez; Victoria R Dimitriades; Morna J Dorsey; Diane J Nugent; Jennifer M Puck; Jasjit Singh; Cathleen A Collins Journal: J Clin Immunol Date: 2021-01-07 Impact factor: 8.542