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-----Original Message-----
From: NIH news releases and news items [mailto:[log in to unmask]] On
Behalf Of NIH OLIB (NIH/OD)
Sent: Monday, December 06, 2004 10:06
To: [log in to unmask]
Subject: NHLBI STOPS STUDY TESTING HOW LONG CHILDREN WITH SICKLE CELL
ANEM IA SHOULD HAVE BLOOD TRANSFUSIONS TO PREVENT STROKE


U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News

National Heart, Lung,
and Blood Institute (NHLBI)
http://www.nhlbi.nih.gov/

EMBARGOED FOR RELEASE
Sunday, December 5, 2004
11:00 a.m. ET

CONTACTS:
NHLBI Communications Office
301-496-4236


NHLBI STOPS STUDY TESTING HOW LONG CHILDREN WITH SICKLE CELL ANEMIA
SHOULD HAVE BLOOD TRANSFUSIONS TO PREVENT STROKE Clinical Alert Issued
to U.S. Physicians

SAN DIEGO, CALIFORNIA -- The National Heart, Lung, and Blood Institute
(NHLBI)
of the National Institutes of Health (NIH) has stopped early a clinical
trial studying whether children with sickle cell anemia at high risk for
stroke could at some point after a minimum of 30 months (range 30-91
months) safely stop receiving the periodic blood transfusions that
prevent strokes. The study found a return to high risk of stroke in
children who stopped receiving the transfusions. The NHLBI is issuing a
clinical alert on the study's results to inform physicians who treat
children with sickle cell anemia.

The alert advises physicians that stopping transfusions cannot be
recommended. The document urges them to carefully discuss with patients
and their families the stroke prevention benefits of continuing periodic
transfusions as well as the risks of these transfusions, which can
include such long-term side effects as iron overload. Management of
these side effects should also be discussed,

according to the alert.

The results of the Stroke Prevention Trial II (STOP II) are being
presented in San Diego today as a special "late-breaking" announcement
at the annual meeting of the American Society of Hematology (ASH). To
further inform physicians, the NHLBI is posting the alert on the
National Library of Medicine's Clinical Alert and Advisories Web page.
STOP II investigators are notifying patients enrolled in the study and
their families.

STOP II, which began in 2000, expected to recruit 100 patients age 2 to
18 over 6 years. When the study was stopped 2 years early on November
10, 79 patients had been enrolled. At the time the study was halted, 14
of the 41 patients who had been randomly assigned to stop transfusions
reverted to high risk of stroke as measured by a special ultrasound
technique and 2 patients had suffered a stroke. There were no strokes or
reversions to high stroke risk in the group

that continued with transfusions.

"This important study shows the value of continuing periodic blood
transfusions in preventing the serious and debilitating consequences of
stroke," said NHLBI Acting Director Barbara Alving, M.D. "At the same
time, there are risks of chronic transfusions and the decision to
continue with this treatment must be made on a case-by-case basis," she
added.

The risks of chronic blood transfusions include iron overload, which can
be harmful to several vital organs and must be treated with chelation
therapy. Other risks include alloimmunization, an immune system reaction
which can interfere with the benefits of subsequent transfusions, and
exposure to
blood-
borne infections.

The STOP II trial, conducted at 23 clinical centers in the U.S. and 2 in
Canada, enrolled patients at increased risk of stroke. Stroke risk was
determined with transcranial doppler (TCD) screening, an ultrasound
technique that measures the velocity of blood flow in the brain. A high
blood flow velocity in one or more major arteries of the brain is linked
with narrowing in key blood vessels supplying the brain, which in turn
increases the risk of a stroke.

STOP II participants had been transfused for at least 30 months before
entering the trial. Eligibility criteria for entry into STOP II were a
normal TCD velocity (indicating low risk of stroke) and a magnetic
resonance imaging study of the patients' brain arteries showing no
severe blockages. Upon entry, patients were randomly assigned to receive
either standard care with periodic blood transfusions or to be taken off
these transfusions.

Patients in the transfusion arm of the study received blood transfusions
every 3 to 4 weeks to keep the amount of abnormal, or sickle, hemoglobin
in their blood to no more than 30 percent of total hemoglobin.
Transfused patients who received a cumulative dose of 250 ml/kg of blood
began to develop iron overload and were given chelation therapy.
Chelation involves subcutaneous infusions of deferoxamine, a drug that
removes the iron.

After 79 patients had been enrolled in the study, the STOP II Data and
Safety Monitoring Board (DSMB), an independent advisory committee
charged with reviewing results and ensuring participant safety,
conducted a regular review of the data. The analysis showed a highly
significant difference in stroke risk and actual stroke between the
transfusion and non-transfusion treatment arms. The DSMB recommended
early closure of the clinical trial.

About 10 percent of sickle cell patients are at risk for stroke. Twenty
percent of patients are at risk for "silent cerebral infarcts," small
strokes that can interfere with cognitive functioning and school
performance because brain tissue is damaged.

The importance of transfusion therapy in preventing strokes in patients
with

sickle cell anemia was established in 1997 when the results of the
Stroke Prevention Trial in Sickle Cell Anemia (STOP I) were released in
a clinical alert. STOP I found that administering blood transfusions
every 3 to 4 weeks to children with sickle cell anemia who are at high
risk for stroke reduces their rate of first-time stroke by 90 percent.

"STOP I showed that we could prevent stroke and its debilitating
consequences, including brain damage. What we didn't know was whether
the transfusions could be safely stopped at some point. This was an
important question because there are some problems with blood
transfusions, including increased risk of iron overload," said Robert
Adams, M.D. principal investigator of both STOP I and

STOP II and Regents Professor of Neurology and Professor of Pediatrics,
Medical College of Georgia. Adams presented the STOP II findings at the
ASH meeting.

"Now we know that for high-risk patients, it is not safe to stop
transfusions even if the TCD has returned to normal range. We need to
weigh carefully the

risks of this preventive therapy and make sure we monitor patients
closely with TCD. We also need to come up with a better way to maintain
the stroke prevention benefit while lowering the side effects of
transfusion treatment," added Adams.

The clinical alert calls for further research to identify and test
therapies

that will provide safe and effective protection from stroke with fewer
side effects than transfusion.

Sickle cell anemia, the most common genetic blood disorder in the U.S.,
affects about 1 in 350 African-Americans and 1 in 1,000 Hispanic
newborns every year. Patients with this disease have abnormal hemoglobin
molecules in their red blood cells. The molecules damage the red cells,
causing them to stick to blood vessel walls. This can lead to narrowed,
or blocked, blood vessels in the brain, causing a stroke.

The participating centers in STOP II were:

Children's Hospital Medical Center; Cincinnati, OH;
Children's Hospital Oakland, Oakland, CA;
Children's Hospital of Los Angeles/UCLA; Los Angeles, CA; Children's
Hospital of New Orleans; Louisiana State University Medical Center, New
Orleans, LA Children's Hospital of Philadelphia; Philadelphia, PA;
Children's Mercy Hospital, Kansas City, MO; Children's National Medical
Center, Washington, DC; Columbia University; New York, NY; Columbus
Regional Hospital, Columbus, GA; East Carolina University, Greenville,
NC; Emory University; Atlanta, GA; Jackson Memorial Hospital, Miami, FL
Johns Hopkins University, Baltimore, MD; Medical College of Georgia;
Augusta, GA; Medical University of South Carolina, Charleston, S.C.;
Morehouse School of Medicine, Atlanta, GA; Rainbow Babies & Children's
Hospital, Cleveland, OH; Scottish Rite Children's Medical Center,
Atlanta, GA; Sinai Hospital of Baltimore; Baltimore, MD; St. Jude
Children's Research Hospital, Memphis, TN; State University of New
York-Brooklyn, Brooklyn, NY; The Hospital for Sick Children; Toronto,
Ontario; University Health Network, Toronto General Hospital, Toronto,
Ontario; University of Alabama, Birmingham, AL; University of
Mississippi Medical Center Children's Hospital, Jackson, MS;

Note: the New England Research Institute, Watertown, MA, was the Data
Coordinating Center

To interview an NHLBI spokesperson about the STOP II study, please call
the NHLBI Communications Office at 301-496-4236. To interview Dr. Adams,
call Toni Baker at the Medical College of Georgia at 706-721-4421. The
clinical alert is online at <http://www.nhlbi.nih.gov>.

NHLBI is part of the National Institutes of Health (NIH), the Federal
Government's primary agency for biomedical and behavioral research. NIH
is a

component of the U.S. Department of Health and Human Services. NHLBI
press releases and fact sheets, including a fact sheet on sickle cell
anemia, can be found online at <http://www.nhlbi.nih.gov>.

##

This NIH News Release is available online at:
http://www.nih.gov/news/pr/dec2004/nhlbi-05.htm

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