Drug wards off sickle-cell attacks.

Federal officials announced this week the first drug therapy that prevents the painful attacks of sickle-cell anemia, an inherited blood disorder that in the United States afflicts mostly blacks of African descent.

Claude Lenfant, director of the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Md., called it "the first effective treatment for this serious illness."

The huzzahs for the drug, hydroxyurea, stem from data collected in an NHLBI-sponsored, multicenter test of its effectiveness. Although scheduled to continue until May 1995, the drug trial was called off on Jan. 14, after a group of independent scientists determined that interim results offered compelling evidence of the drug's value. NHLBI's decision to halt the study means that physicians can now offer all patients the option of hydroxyurea treatment.

Investigators at 21 medical centers across the United States began the trial by recruiting 299 people with moderate to severe sickle-cell disease. All the volunteers were age 18 or older and had experienced at least three sickle-cell crises in the year prior to enrollment. Half the recruits received hydroxyurea; half got an inactive substance, or placebo.

The interim results revealed a dramatic benefit from drug therapy. Daily treatment with hydroxyurea reduced by half the number of sickle-cell episodes.

People with this disorder suffer periodic attacks in which their red blood cells form a characteristic crescent shape. An abnormal hemoglobin, or pigment, in these cells lies at the root of the problem. After releasing the oxygen they carry, hemoglobin molecules are supposed to remain separate. But in sickle-cell anemia, they form rigid rods that prevent the red blood cell from remaining pliable.

These sickle-shaped cells then clog the body's small blood vessels and block the distribution of life-giving oxygen, an exceedingly painful event that can cause organ damage.

Until now, doctors had to rely on palliatives such as painkillers and blood transfusions to treat symptoms of the disease. But these measures didn't attack the underlying problem.

"The patients treated with hydroxyurea also required about 50 percent fewer blood transfusions during the study," noted study chairman Samuel Charache of the Johns Hopkins University School of Medicine in Baltimore. In addition, the drug significantly reduced a complication of the disease in which patients develop severe chest pain and fever, he said.

Researchers don't fully understand why hydroxyurea works. But they suspect it boosts the body's supply of fetal hemoglobin, a type of hemoglobin produced by fetuses and newborns that does not form stiff rods inside red blood cells. Normally, adults make only tiny amounts of this variation of hemoglobin.

The Food and Drug Administration has already approved the drug as a treatment for polycythemia vera, a disease in which the body makes too many red blood cells. Thus doctors can now prescribe hydroxyurea for their patients even though the compound has yet to pass FDA muster specifically as a treatment for sickle-cell disease.

However, researchers offered patients a warning. "Hydroxyurea is not a cure," Charache says. "It has beneficial effects, but they last only as long as the patient continues to take the prescribed dose."

They also caution that not every sickle-cell patient should get the drug, which can cause serious side effects.

"Hydroxyurea is a cytotoxic agent," Charache says, noting that it has been linked with leukemia in some polycythemia vera patients. In addition, the trial collected data only on adult patients. For now, scientists advise against giving the powerful medication to children.