Long-term results of bone marrow transplantation in complete DiGeorge syndrome.
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Land
Michael H
MH
Department of Pediatrics, University of California at Los Angeles Medical Center, Los Angeles, CA 90095, USA.
Garcia-Lloret
Maria I
MI
Borzy
Michael S
MS
Rao
P Nagesh
PN
Aziz
Najib
N
McGhee
Sean A
SA
Chen
Karin
K
Gorski
Jack
J
Stiehm
E Richard
ER
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D016516:CD4-CD8 Ratio; D004062:DiGeorge Syndrome / Q000276:immunology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D013601:T-Lymphocytes / Q000276:immunology