Innovative Procedure for DiGeorge Syndrome
Duke Children’s Hospital is the only U.S. medical center offering thymus transplantation to infants born with complete DiGeorge syndrome. This rare immune disorder is characterized by the lack of a thymus, the small gland near the heart that generates infection-fighting T cells. We strive to give your child the best chance to develop a strong immune system for a healthy life.
What is the Thymus?
The thymus is like a school house attended by stem cells, immature white blood cells from bone marrow, that develop into functioning T cells. In about six months, a small percentage of the developing T cells leave the thymus to become normal T cells that protect the infant by fighting off infection and not attacking the infant’s organs.
When the thymus is present at birth, it is located on top of the heart. If an infant with a thymus requires heart surgery, the surgeon may remove a portion of the thymus to operate on the part of the heart that is underneath the thymus. This discarded thymus tissue may be used for thymus transplantation after permission is obtained from the infant’s parent(s).
What is Thymus Transplantation?
Thymus transplantation is an investigational procedure that uses thin slices of thymus tissue to build the immune system of an infant born without a thymus. This can occur when a child is born with complete DiGeorge syndrome, a condition that can also cause other medical concerns, including a heart defect and/or calcium problems. Some infants with DiGeorge may have a genetic abnormality, and problems with vision and hearing, blockage of one or both nasal passages, and abnormal ears.
The donor thymus used for thymus transplantation is cut into thin slices and kept in the laboratory while testing is done on blood from the infant’s mother and from the infant. The testing ensures the thymus donor does not have an infection that could harm the infant with complete DiGeorge syndrome. The thin slices of thymus tissue are then implanted into the thigh muscle of an infant born without a thymus who has complete DiGeorge syndrome. Once in place, tiny blood vessels called capillaries grow from the muscle into the thymus tissue providing oxygen and nutrients. If the procedure is successful, the infant develops T cells that can fight infections within about six to nine months.
Unparalleled Expertise in Thymus Transplantation
- Since developing thymus transplantation in 1992, Duke pediatric immunologists have performed more than 90 thymus transplants, primarily in infants with complete DiGeorge Syndrome. The overall survival rate is 71 percent.
- Our pediatric immunology team trained specialists in the United Kingdom, which is now the only other medical center in the world performing thymus transplants.
- The investigational biologic therapy used in the transplant process, RVT-802 (licensed to Enzyvant Therapeutics GmbH), recently received Breakthrough Therapy designation and Regenerative Medicine Advanced Therapy designation from the FDA, conferring “special access to the Office of Tissues and Advanced Therapies for development guidance as well as expedited review pathways.”
- Our thymus transplant team includes many specialists who provide compassionate care to your child and works closely with your child’s referring doctors to ensure individualized care. We guide you through the process and support your child’s recovery.
- Our pediatric immunologists are dedicated researchers who are constantly striving to better understand disorders such as complete DiGeorge syndrome, and the long term outcomes for children who have undergone thymus transplantation. This work helps guide our approach to thymus transplantation.
A written physician referral is required for your child to be considered for the thymus transplant. Please contact Stephanie Gupton.
Duke’s Thymus Transplantation Clinical Review Committee will determine whether your child is a candidate for transplantation. Once the committee agrees that your child could benefit from a thymus transplant, a financial review is performed. Depending on insurance and the state you are living in either your referring doctors or the Duke team will request authorization to perform the thymus transplant. Because thymus transplantation is still an investigational procedure, many insurance companies initially deny authorization. The Duke team and your doctors then file an appeal; we have been very successful with the appeals so far. After authorization is obtained, an agreement is signed to allow your child to come to Duke. You will be informed when this is completed. The committee will determine the order in which children come to Duke for transplantation.
After the committee review and prior to coming you will receive a consent document that will be reviewed with you so you understand all the procedures, risks, and benefits prior to coming to Duke for the transplant.
Once Approved for Thymus Transplant
You will need to stay in or near Duke for about two months for your child to obtain the thymus transplant. Depending on your child’s clinical condition, your child may be able to be an outpatient for most of the time while in the Durham area.
If your child needs hospitalization or care in a Pediatric Intensive Care Unit, your child will be an inpatient while at Duke. It is expected that a parent or other adult will stay with the child 24/7 if on the bone marrow transplant unit or a minimum of 8 hours a day in other units. There are no funds for food or housing for adult caretakers while their child is in the Durham area or in the hospital. There is no funding for supplies such as diapers. Parents should talk with their insurance company about whether there will be co-pays for clinic visits, and whether outpatient medications can be obtained from the Duke Children’s Pharmacy or if family members back home will have to pick up prescriptions from a local pharmacy and send them to you by express mail. If your child requires tube feeding or other home health supplies, these items may not be covered by insurance. Fund raising can be done prior to coming to Duke for these expenses.
After coming to Duke, your child will undergo a complete medical evaluation with blood work and imaging tests. At the same time, we start screening for thymus tissue. When thymus tissue becomes available, we begin to process the tissue and test for infections. While most organ transplants require blood type compatibility (matching) between recipient and donor, children under the age of 2 years usually haven’t developed antibodies against other blood and tissue types so matching is not typically required. You will be notified when suitable tissue is available for your child.
Thymus transplantation is done in the operating room. A pediatric general surgeon makes a cut in the skin to expose the thigh muscle. Between 10 and 40 thymus tissue slices are put into little pockets created in the thigh muscle in one or both legs. After surgery, your child goes to the recovery room and then to the Pediatric Bone Marrow Transplant Unit for care.
About half of children who come to Duke have no T cells and do not need immunosuppression. If they are outpatients, they may only be in the hospital for 1 to 3 nights after the transplant. The other half of children usually need to be on immunosuppression medication for nine to 12 months after transplantation. They need additional mediation prior to the transplant to prevent uneducated T cells from attacking the thymus. These children are usually in the hospital for approximately 10 days.
If your child is stable, he/she will return to the care of the referring immunologist/facility one to two weeks after thymus transplantation. Our thymus transplant team maintains close consultation with the referring medical team during the first year as T cells are developing.
Your child will need to continue in isolation for about one year after transplantation to protect him or her from contracting infections. Your immunologist will send blood to Duke approximately every three months for the first year after transplantation to monitor the development of infection-fighting T cells—a process that may take six to nine months.