Hydroxyurea treatment for sickle cell underused by doctors

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," says Sophie Lanzkron, M.D., assistant professor of medicine and oncology at the Johns Hopkins University 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, they 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, the researchers say, is a clear picture of the drug's effectiveness.

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 to 84 percent in people taking hydroxyurea. Their hospital admissions declined by 18 to 32 percent.

On the biological side, amounts of fetal hemoglobin, a blood component that seems to decrease sickle cell symptoms, increased by 4 to 20 percent after patients began taking hydroxyurea.

On the negative side of the risk/benefit ledger, studies in mice also 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 in the June 17 Annals of Internal Medicine, they 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 says.

Sickle cell anemia, an inherited disorder that affects mostly people of African and Hispanic heritage, is named for the crescent- or sickle-shaped blood cells caused by the disease. The C-shaped 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 U.S. Department of Health and Human Services.

Other Hopkins researchers who participated in this research include John J. Strouse, M.D.; Renee Wilson, M.Sc.; Mary Catherine Beach, M.D., M.P.H.; Carlton Haywood, M.A.; HaeSong Park, M.D., M.P.H.; Katherine Witkop, M.D., M.P.H.; Eric. B. Bass, M.D., M.P.H.; and Jodi B. Segal, M.D., M.P.H.