Jan. 29, 2002 DURHAM, N.C. -- When performed within the first 28 days of birth, stem cell transplants have a 95 percent success rate in treating newborn babies with severe combined immunodeficiency (SCID), according to a long-term study by Duke University Medical Center researchers.
Additionally, when babies who receive these early transplants are compared with those who received the same transplants after the first four weeks of life, the earlier transplants appear to stimulate a more robust and effective immune system. This enhanced response may be due to reduced stresses on the thymus, an organ responsible for "training" immature immune cells to fight off disease, said the researchers.
The results of the Duke study, which was supported by the National Institutes of Health (NIH), were published today (Jan. 24) in the February issue of the journal Blood.
SCID is a rare disorder in which babies are essentially born with little or no immune system, leaving them unable to defend themselves from potentially life-threatening infections. The stem cells used for transplant are obtained from the bone marrow of related donors and infused into the baby to generate a "new" immune system.
During the past 19 years, the Duke team has performed stem cell transplants on 117 SCID patients. Of the 21 babies who received their transplants within the first 28 days of life, 20 are still alive and leading normal lives, the oldest being 19 years old, said the Duke researchers. For those 96 babies who received their transplants after 28 days, the survival rate is 73 percent.
"By transplanting these children very early, we were able to provide an immune system to protect them from opportunistic infections," said Duke pediatric immunologist Dr. Laurie Myers and lead author of the new analysis. "We have shown that by transplanting early, we can improve the survival rates of an already highly effective therapy.
"Twenty years ago, all of these babies would have died," Myers added. "A pathogen that would have little effect on a healthy baby could kill one with SCID."
The key to improving the chances of a baby with SCID lies in early detection. According to Myers, all that is required is a simple test after birth in which researchers count the number of lymphocytes, a type of white blood cell, in a blood sample. However, she added, since the incidence of SCID ranges from one in 50,000 to 100,000 births, most pediatricians do not routinely order lymphocyte counts for this rare disorder.
"If, however, there is a family history of SCID, most parents want their baby tested," Myers said. "In our study, we identified nine of the 21 babies before birth and 12 immediately after, and in all cases there was a family history, so we were able to do the transplant shortly after birth."
On average, babies are first diagnosed with SCID after the age of 6 months. By that time the baby has probably suffered many infections and has not thrived as healthy babies would, Myers said. One effect of these repeated infections, the researchers believe, is undue stress on the thymus.
The thymus is critical in the development of key immune system cells known as T cells. These potent cells begin life in the bone marrow as stem cells, then migrate to the thymus where they divide, mature and receive their "marching orders" for the defense of the body.
"Researchers believe babies with SCID who are transplanted earlier have a thymus that hasn't been stressed by infections and so can turn the donated stem cells into functioning T cells," Myers said. "In the babies with early transplants, we saw a significantly higher number of T cells, and this was most evident from three months to three years after transplantation, a critical time in the development of defenses against common childhood infections."
The transplant itself is relatively straightforward. Physicians begin by removing bone marrow cells from the donor's hip. Researchers then remove the donor's mature T cells to avoid a condition known as graft-vs.-host disease, in which the donor's immune cells attack the recipient. The resulting stem cells are then infused into the baby.
"The cells know where to go, and eventually go to the thymus," Myers explained. "Within one month, we can see a significant increase in the number of new immune cells, and by three months, the levels are normal. Those who received the transplants in the first 28 days had more T cells earlier."
The Duke SCID program, which is one of the few in the country specializing in this treatment, was developed and is led by Dr. Rebecca Buckley, chief of pediatric allergy and immunology.
Other authors on the paper were Duke's Dr. Dhavalkumar Patel and Dr. Jennifer Puck of the NIH.
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