Uncertainties about proper use and possible long-term
effects of hydroxyurea in the treatment
of sickle cell anemia may be wrongly influencing doctors to
avoid prescribing it to those in serious
need, according to results of a literature review by
specialists at Johns Hopkins.
"We know that many people with sickle cell disease
aren't being offered this drug, which is the
only one we have to treat this disease," said Sophie
Lanzkron, assistant professor of medicine and
oncology at the School of Medicine and director of the Sickle Cell Center
for Adults at Johns Hopkins.
In a bid to heighten awareness about the nature of the
uncertainties and correct clinical use of
the drug, the U.S. Department of Health and Human Services
selected Lanzkron and her colleagues at
Johns Hopkins to gather information from previously
published studies on hydroxyurea.
First, the researchers combed through databases to
select randomized clinical trials,
observational studies and case reports that evaluated the
drug's effectiveness and incidences of toxic
side effects. They excluded the poorer quality data and
non-English publications and carefully
analyzed data from 246 articles.
What emerged, they say, is a clear picture of the
Specifically, they found that the number of intensely
painful sickle cell "crises" — caused when
misshapen, "sickled," red blood cells clump in blood
vessels — dropped by 68 percent to 84 percent in
people taking hydroxyurea. Their hospital admissions
declined by 18 percent to 32 percent. On the
biological side, amounts of fetal hemoglobin, a blood
component that seems to decrease sickle cell
symptoms, increased by 4 percent to 20 percent after
patients began taking hydroxyurea.
On the negative side of the risk/benefit ledger,
studies in mice indicated that hydroxyurea
impairs sperm development; the researchers concluded that
this effect could be present in human
patients as well. The review could not conclude with any
confidence that hydroxyurea increased or
decreased the risk of leukemia or other tumors, leg ulcers
and pregnancy complications.
In the team's report, published June 17 in the
Annals of Internal Medicine, the researchers
conclude that hydroxyurea be considered a viable treatment
option, but emphasized the need for
more quality research.
"It's clear from our literature review that
hydroxyurea works, but we need to do much more
work to understand how it works and the best ways to use
it," Lanzkron said.
Sickle cell anemia, an inherited disorder that affects
mostly people of African and Hispanic
heritage, is named for the sickle-shaped blood cells caused
by the disease. The cells periodically clump
inside blood vessels, blocking circulation and causing
severe anemia, increased risk of infections or
strokes and episodes of extreme pain that can last hours or
days. About 70,000 people have sickle cell
disease in the United States.
This research was funded by the Agency for Healthcare
Research and Quality, part of the
Department of Health and Human Services.
Other Johns Hopkins researchers who participated in
this research are John J. Strouse, Renee
Wilson, Mary Catherine Beach, Carlton Haywood, HaeSong
Park, Katherine Witkop, Eric. B. Bass and
Jodi B. Segal.