Feb. 19, 1999 DURHAM, N.C.- After 16 years of perfecting an experimental treatment, doctors at Duke University Medical Center report they can save most babies born with a rare and fatal immune disorder by giving them a family member's bone marrow within the first 3 1/2 months of life.
All but one of 22 babies who received a transplant in this time frame survived, according to results of a study published in the Feb. 17 issue of the New England Journal of Medicine.
Without a timely transplant, infants with severe combined immune deficiency (SCID) are destined to die within a year, overcome by infections that attack their bodies because they lack an immune system, said Dr. Rebecca Buckley, chief of Duke's division of pediatric allergy and immunology.
Giving them a bone marrow transplant soon after birth allows them to build a healthy immune system before opportunistic infections can take hold and jeopardize the success of the transplant. Early treatment also reduces the cost of care by hundreds of thousands of dollars. A transplant within the first few months can cost less than $30,000, whereas waiting until the child is seriously ill can boost the price tag into the millions and may fail, Buckley said.
Taken together, Buckley's approach has eradicated the need for toxic chemotherapy, sterile environments and lengthy hospital stays that once typified the ordeal of children with "bubble boy" disease, the term assigned to David Vetter, a young Texas patient who lived for 12 years in a plastic, germ-free bubble and died in 1984. Children can now be treated as outpatients without a hospital stay.
"This once-fatal disease should be seen as a pediatric emergency that requires immediate diagnosis and treatment because now there is a proven therapy that can save a child's life," Buckley said in an interview.
Buckley's program has yielded the highest reported success rate in the world and appears to provide a full cure for many children and a partial cure for others -- mostly depending on the patient's genetic mutation and the donor's genetic compatibility to the patient. Of all 89 children she has treated, including those diagnosed well after the first months of life, 72 are alive and faring well, some of them for more than 16 years after their transplants, the report said.
Their survival is largely due to Buckley's novel approach to administering bone marrow transplants. By cleansing the donor marrow of its T-cells, Buckley has diminished the potentially fatal complication called graft-versus-host disease, in which the donor marrow rises up to attack its new host. Without T-cells, the donor marrow doesn't recognize its foreign surroundings and more easily adapts to its new home.
The benefits of this approach are many, Buckley said. First, the infant is spared the toxic "anti-rejection" drugs normally given to suppress the donor's T-cells.
Second, and more importantly, T-cell depletion opens the door for dozens more infants to be saved each year, meaning that a full genetic match is no longer required for successful transplant. A half-matched donor will do.
"Until 1982, SCID was invariably fatal unless the patient had a brother or sister who was an exact genetic match to the patient," Buckley said. "What we now know is that, while a perfectly matched sibling is preferable, it isn't a requirement. As long as we remove the T-cells from the parent's marrow, their half-matched bone marrow won't attack the patient's vital organs."
Called "half-matched" donors because each parent contributes half of his or her genetic material to the infant, this type of transplant has now become the standard for treating children with SCID who do not have a matched sibling, said Buckley. Seventy-seven of the 89 children in Buckley's study received their parent's bone marrow, and 60 of them have survived.
Successful treatment depends on several factors, including the particular mutation that caused SCID. Researchers have identified five genetic defects that can cause SCID, all of them leading to a lack of T or B immune cell function, which is essential for protection against infection.
But the very defect that makes patients vulnerable to infection is also of some benefit during treatment, Buckley said. Because they have no T-cells, SCID patients do not require chemotherapy to destroy them, as is the case with cancer patients.
"Patients with SCID have no immune systems to reject the transplants. Our approach avoids chemotherapeutic toxic agents and all their complications," said Buckley.
Buckley aids the recovery of her patients by bolstering them with approximately 20 times the amount of bone marrow stem cells than other centers deliver, a technique that speeds their ability to "grow" an immune system from their donor cells.
What has lagged behind treatment, Buckley says, is the rapid and early diagnosis needed to screen children with SCID before they are overcome by simple infections.
Even now, early diagnosis of SCID is rare because doctors do not routinely perform a test in newborns to count a type of white blood cell called lymphocytes. Such a test could screen for children with SCID as well as those with other serious immune deficiencies that would not be apparent until the child developed an infection. Although rare -- the defect is estimated to occur once in every 500,000 births -- the cost to save a child would be no more than $41 per child, Buckley said.
"A simple blood test could allow us to treat, and most likely cure, SCID in a child for as little as $30,000," Buckley said. "If found later, less effective treatment can run into the millions, and it might be too late to save the child."
In the future, Buckley said she hopes that gene therapy can be perfected to restore B-cell function, a component of the immune system not corrected by bone marrow transplantation in some SCID children.
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