Duke Doctors can now Cure Most Babies Born with Fatal Immune Disease
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
"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."