Breakthrough: Baltimore woman becomes one of the first adults to be
cured of sickle-cell disease
By Stephanie Desmon
THE BALTIMORE SUN
Published: April 29, 2008
BALTIMORE -- Fifteen months ago, the pain from Pamela Newton's sickle-
cell disease was excruciating. She spent more time in the hospital
than in her apartment. She was on 15 pain pills a day, all heavy
narcotics. She was bleeding regularly and needed daily transfusions
of platelets.
She had just months to live.
Today, doctors at Johns Hopkins Hospital say that Newton, 35, is one
of the first adults in the world to be cured of sickle-cell disease --
and the first using an experimental bone-marrow transplant that
could cure thousands like her who have been told they will never get
better.
Word of a breakthrough gives hope to the roughly 80,000 Americans --
and millions around the world -- who suffer from this debilitating
and usually fatal disease, which is predominant among blacks and
Hispanics.
"It could very much open things up," said Dr. John F. Tisdale, a
senior investigator at the National Heart Lung and Blood
Institute. "Everyone's cautiously optimistic."
What makes the Hopkins procedure different is that it allows patients
to receive bone marrow from a donor who is not an exact match -- a
longtime obstacle to healing large numbers of people.
Sickle cell is an inherited blood disorder that affects red blood
cells. Normally round, the cells become "C" shaped, like sickles, and
pile up on one another, keeping them from properly supplying oxygen
to the body. The patients, prone to infection and serious pain,
typically live only into their 40s.
Until now, few have been cured, and there has been little progress in
developing new treatments. Only one drug has been approved for
treatment of sickle cell. Painkillers and antibiotics help patients
live longer, but nothing has addressed the core problem of the
genetic defect.
Newton's hematologist, Dr. Robert Brodsky, and his colleagues say
they hope to change that. They are trying to enroll 25 patients in a
clinical trial.
Still, the procedure is not without risk. When performed on patients
with leukemia and other diseases, it has a mortality rate of 16
percent.
"We may shorten people's lives, but this is their only chance for a
cure," Brodsky said. "Would you offer this to every sickle-cell
patient? Absolutely not. But the patient who is ending up in the
emergency room three and four times a month and having organ-
threatening and life-threatening complications from the disease ...
should be able to make that decision."
Critics say that the risk associated with the Hopkins procedure is
too high, even for a small trial. They say that most sickle-cell
patients aren't likely to die immediately without a bone marrow
transplant.
"I don't think the time is right yet to go ahead with such
transplants at full tilt," said Dr. Rainer Storb, an oncologist at
Fred Hutchinson Cancer Research Center in Seattle, which cured
several children with sickle cell using bone-marrow transplants
during the 1990s.
Bone-marrow transplants have been used to treat sickle-cell disease
for 20 years, but almost all of the 200 cured have been children. The
treatments rely on high doses of chemicals that knock out the
patient's own marrow before the transplant and are so toxic that
adults with sickle cell-induced organ damage would be unlikely to
survive.
Brodsky said that his team's procedure, developed by Drs. Ephraim
Fuchs and Leo Luznik, is less toxic. They no longer believe that they
have to destroy as much of the patient's marrow as they once did, so
they administer just enough chemotherapy to suppress the immune
system. That dose keeps patients from rejecting the new marrow
without harming their organs.
This change allows transplants for adults as well as children.
Because the procedure is used later in life, it relieves parents of
the burden of making the decision for their youngsters (even in
children, the sickle-cell transplant mortality rate is 5 percent to
10 percent). Instead, it allows the adult patient to see how severe
the disease is before deciding whether to have a transplant.
Another transplant obstacle has been finding a perfect bone-marrow
match. A full sibling's marrow provides the best chance, but there's
only a 25 percent chance that even a full sibling will be a match.
And since sickle cell is inherited, siblings may also have the
disease. That leaves about a 10 percent chance that a patient will
find a suitable donor.
Brodsky's procedure requires just a half-match, meaning that children
and parents of the patient could be suitable donors.
Three days after the transplant, the patient is given a high dose of
a drug called cyclophosphamide. Just as the bone marrow is taking
root, the drug kills off the donor's lymphocytes, the blood cells
that are part of the immune system.
The cyclophosphamide spares the donor's stem cells and allows them to
establish new blood cells and a new immune system. The nascent immune
system is retrained to see the patient's body as friend, not foe.
This prevents the patient from rejecting the transplanted bone marrow
and prevents the newly developing immune system from attacking the
patient.
Brodsky compares the drug's effect to rebooting a
computer: "Cyclophosphamide is control-alt-
system."
With a new immune system, the foundation is laid for the donor stem
cells to out-compete the patient's weakened stem cells. Healthy blood
cells are created and start circulating, overtaking the sickle blood
cells.
Brodsky said that the biggest problem in promoting widespread use of
his new procedure may be the cost. Most insurance companies won't
cover experimental treatment for genetic disorders, he said.
At the National Heart Lung and Blood Institute, Tisdale and his team
began testing a new bone-marrow-
years ago. Of eight transplanted adults, seven were cured. The eighth
patient survived the transplant, but his symptoms returned.
Despite his investment in his own procedure, Tisdale said that the
Hopkins method would be a "huge" breakthrough if it works in more
patients because it only requires half matches, while his requires
full matches.
The Hopkins procedure has been a life-saver for Pamela Newton.
Early on, Newton's mother knew something was wrong with her baby. She
cried a lot, especially when she was picked up. When she learned to
walk, she dragged her legs. Her mother took her back and forth to
hospitals until she was 5, when a doctor finally ordered the critical
blood test. She had sickle cell.
Newton needed an extra year to graduate from high school after
missing too many classes when she was sick. She dropped out of
college when the pain, which she said felt like a heart attack all
over her body, made it too hard to focus. By then she needed regular
narcotics and used a Demerol pump. She spent 15 years on daily
painkillers, sometimes going to the hospital twice a month.
By 2006, when she was referred to Brodsky, Newton was out of options.
Brodsky offered her a bone-marrow transplant. He warned her of the
risks. He told her she could die.
"He made it very clear. This is not something you can enter into
lightly," she recalled.
But, she said, "the transplant was my only hope."
The mother who had given Newton life once before gave her life again,
becoming the bone marrow donor.
Two months after the transplant on Dec. 29, 2006, Newton started to
feel better. Slowly, gradually, the pain dissipated. She took her
final OxyContin last April.
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becomes-one-
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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