Thymus Transplantation in DiGeorge Syndrome
Summary
The purpose of this study is to determine whether thymus transplantation without immunosuppression is effective in treating typical DiGeorge syndrome.
Description
There is no safe and effective treatment for DiGeorge syndrome and most patients die by the age of two. For patients with a severe T cell defect, the PI has shown that thymus transplantation is safe and efficacious under other clinical protocols. Complete DiGeorge syndrome is characterized by very low T cell or very low naïve T cell numbers. In this study, typical complete DiGeorge syndrome subjects receive human postnatal cultured thymus tissue transplants. Thymus tissue that would otherwise be discarded is transplanted into DiGeorge subjects in the operating room. At the time of transplantation, a skin biopsy is obtained look for any preexisting T cells. After transplantation, subjects are followed by routine research immune evaluations, using blood samples obtained every 2-4 weeks. At approximately 2-3 months post-transplantation subjects undergo an open biopsy of the allograft. The biopsy is done under general anesthesia in the operating room. At the time of the graft biopsy, another skin biopsy is obtained to look for clonal populations of T cells.
The protocol aims include: assessing thymopoiesis in the allograft biopsy; assessing immunoreconstitution of complete DiGeorge syndrome subjects after postnatal allogeneic thymus transplantation; assessing minimally invasive methods of assessing thymopoiesis (flow cytometry and polymerase chain reaction (PCR)); assessing pre-transplant T cells which do not proliferate in response to mitogens (focusing on NK-T cells); and, assessing thymus transplantation safety and toxicity.
Study Design
Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
DiGeorge Syndrome
Intervention
Thymus Transplantation
Location
Duke University Medical Center
Durham
North Carolina
United States
27710
Status
Recruiting
Source
Duke University
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00576407
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
22q11 Deletion Syndrome
Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.
Transplantation Immunology
A general term for the complex phenomena involved in allo- and xenograft rejection by a host and graft vs host reaction. Although the reactions involved in transplantation immunology are primarily thymus-dependent phenomena of cellular immunity, humoral factors also play a part in late rejection.
Thymus Hyperplasia
Enlargement of the thymus. A condition described in the late 1940's and 1950's as pathological thymic hypertrophy was status thymolymphaticus and was treated with radiotherapy. Unnecessary removal of the thymus was also practiced. It later became apparent that the thymus undergoes normal physiological hypertrophy, reaching a maximum at puberty and involuting thereafter. The concept of status thymolymphaticus has been abandoned. Thymus hyperplasia is present in two thirds of all patients with myasthenia gravis. (From Segen, Dictionary of Modern Medicine, 1992; Cecil Textbook of Medicine, 19th ed, p1486)
Digeorge Syndrome
Congenital syndrome characterized by a spectrum of malformations including the absence of the THYMUS and PARATHYROID GLANDS resulting in T-cell immunodeficiency and HYPOCALCEMIA. Other features include defects in the outflow tract of the HEART and craniofacial anomalies (velocardiofacial syndrome). Most cases result from a deletion of chromosome 22q11.2 or mutation in the TBX1 gene.
Transplantation Conditioning
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
Clinical Trials
Thymus Transplantation Dose in DiGeorge
One purpose of this study is to determine whether the amount of thymus tissue transplanted into DiGeorge syndrome infants has any effect on the immune outcome. Another purpose of this stud...
Thymus Transplantation With Immunosuppression
The purpose of this research is to determine if thymus transplantation with immunosuppression is a safe and effective treatment for complete DiGeorge syndrome. The research will include st...
Phase I Thymus Transplantation With Immunosuppression
The purpose of this study is to determine if thymus transplantation with immunosuppression is a safe and effective treatment for atypical complete DiGeorge syndrome. This study will also e...
Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
OBJECTIVES: I. Determine the pattern of immunologic reconstitution in patients with T-cell compromise due to DiGeorge syndrome or velocardiofacial syndrome. II. Determine any cor...
Phase I Study of Umbilical Cord Blood Transplantation Followed by Third Party Thymus Transplantation
The objective of this trial is to assess the toxicity of thymus transplantation following unrelated umbilical cord blood transplantation. Emphasis will be placed on adverse events that ar...
PubMed Articles
Clinical and immunophenotypic features of atypical complete DiGeorge syndrome.
BACKGROUND: DiGeorge syndrome is a congenital malformation characterized by variable defects of the thymus, heart and parathyroid glands. Athymic patients are classified as exhibiting complete DiGeorg...
BACKGROUND: The induction of tolerance toward third-party solid organ grafts with allogeneic thymus tissue transplantation has not been previously demonstrated in human subjects. OBJECTIVE: Infants wi...
A 30-year-old nulliparous woman was seen for a detailed ultrasound scan at 20 weeks of gestation. The scan revealed a male fetus with truncus arteriosus, membranous ventricular septal defect, absent...
Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of CHARGE patients show overlapping phenotypic characteristics with DiGeorge syndrome (thymic hypo/aplasia, hypocalcemia, T-c...
Hematopoietic stem cell transplantation: Targeting the thymus.
Allogeneic hematopoietic stem cell (HSC) transplantation can cure patients suffering from diverse genetic and acquired diseases as well as cancers. Nevertheless, under conditions where T cell reconsti...
