Reunion spurs follow-up study on treatment for DiGeorge syndrome - Findings show efficacy of bone marrow transplantation
More than 20 years ago, doctors at Mattel Children's Hospital UCLA performed a successful bone marrow transplant on a baby girl who was born without a thymus gland and was suffering from severe immune deficiency. It marked the first time a bone marrow transplant, rather than a thymic transplant, had been used to treat the genetic condition known as DiGeorge syndrome (DGS).
The doctors lost track of the young girl when her family moved away but were reunited with her when she returned to UCLA for heart treatment in 2005. Upon rechecking the young woman's immune system, they were pleased to learn that she continued to do well.
Inspired by her positive long-term outcome - along with a handful of other DGS bone marrow transplant patients worldwide - UCLA researchers embarked on a study to follow up on the benefits of bone marrow transplant treatment. Their findings are published in the October 2007 issue of the peer-reviewed Journal of Allergy and Clinical Immunology.
Overall, the researchers found that survival with bone marrow transplant was greater than 75 percent, similar to thymic transplantation.
"We believe that this long-term follow-up study indicates that bone marrow transplant is a good procedure - and more readily available than thymic transplantation - for complete DiGeorge syndrome," said co-author Dr. E. Richard Stiehm, professor of pediatrics in the division of immunology, allergy and rheumatology at Mattel Children's Hospital UCLA. "This also suggests that the thymus may not be necessary for immune development after birth, or that other tissues, such as the skin, may serve as a thymus equivalent."
DiGeorge syndrome is a common genetic immunodeficiency that occurs in one out of every 2,000 people. The syndrome includes thymic and parathyroid deficiency, chromosome abnormalities, low calcium levels and decreased immunity. Patients often have heart problems and developmental delay, which bone marrow or thymic transplants do not correct. Only a few patients have the severely deficient immune systems characteristic of complete DGS, which is similar to severe combined immunodeficiency (also known as "bubble boy syndrome") and is fatal if untreated.
In this first report of extended survival in patients with complete DGS who were treated with bone marrow transplant with long-lasting immune reconstitution, researchers described the medical history and current immune function of two DGS patients who received transplants more than two decades ago. Now in their 20s, both patients lead normal lives free of serious infections and have preserved immune function.
The study also reviewed nine additional cases from other centers internationally and assessed the current status of all patients but one.
The thymus produces hormones that stimulate the production of certain infection-fighting cells. It is also of central importance in the maturation of T-cells (thymic cells), which help build immunity.
According to Stiehm, the thymus gland is the "university" of the immune system.
"Stem cells must go there to be educated before entering the circulation to fight organisms," he said. "The thymus continues to put out T-cells for a lifetime. It puts out naive T-cells that are then exposed to microbes to become memory T-cells. It was previously thought that the body needs a continuous supply of new naive cells to keep the immune system functioning, but now we think that maybe it's not necessary, since the memory cells from the donor may serve for a lifetime."
The significance is that adult memory cells from bone marrow, or peripheral blood, can persist in the circulation for several decades and keep the patient well, even though new naive T-cells from the thymus are not produced.
A bone marrow transplant works by replacing the patient's marrow with healthy marrow from a matched donor. Ultimately, the new marrow helps the patient produce normal blood cells.
A thymic transplant is an effective but complicated procedure that involves transferring the thymus tissue of another infant undergoing heart surgery, culturing it, and then surgically implanting it in the patient. It then takes several months for the thymus gland to grow and allow the patient to develop a functioning immune system.
Thymus transplantation is available in the U.S. only at Duke University's medical center. By contrast, bone marrow transplant is a standard procedure available at many large medical centers across the country and internationally.
In addition to Stiehm, study authors included Michael Henry Land, Maria Ines Garcia-Lloret, Michael S. Borzy, P. Nagesh Rao, Najib Aziz, Sean A. McGhee, Karin Chen and Jack Gorski. There are no financial disclosures to report.
Mattel Children's Hospital UCLA, one of the highest-rated children's hospitals in Southern California, is a vital component of UCLA Medical Center, which was recently ranked as the third best hospital in nation and best in the western United States by U.S. News & World Report. Mattel Children's Hospital offers a full spectrum of primary and specialized medical care for infants, children and adolescents. The hospital's mission is to provide state-of-the-art treatment for children in a compassionate atmosphere, as well as to improve the understanding and treatment of pediatric diseases. For more information, visit www.uclahealth.org/mattel.