A new treatment for sickle cell anemia -- a drug that reduces the anemia and helps prevent the painful "crises" that mark the disease -- has shown promise in a small, preliminary study of three patients with the disease.
In people with sickle cell anemia, red blood cells contain an abnormal form of hemoglobin, the oxygen-carrying protein, that can distort cells from their normal bagel shape into a crescent or sickle shape, making them unusually fragile and often leading to painful blockages of blood vessels.
A report in today's issue of the New England Journal of Medicine is the first to show that the drug, hydroxyurea, can improve the survival of red blood cells and reduce pain in people with the disease. About 50,000 Americans have sickle cell anemia.
The drug works by increasing the body's production of another form of hemoglobin that is normally produced during fetal life. After birth, the gene for fetal hemoglobin gradually slows down and a different gene, for adult hemoglobin, takes over. Even in patients with sickle cell disease, however, the fetal hemoglobin gene is normal and remains available. It is not known why hydroxyurea switches the fetal gene back on.
Hydroxyurea has been used for about 15 years to treat chronic leukemia and other blood disorders sometimes seen in elderly people. The report's authors said they were excited by the findings, but cautioned that before hydroxyurea becomes widely used for sickle cell anemia, their results need to be confirmed in a much larger, multi-hospital study that would compare the drug with a placebo.
The study by researchers at Harvard and Johns Hopkins medical schools enrolled five patients with severe sickle cell anemia to test hydroxyurea and erythropoietin, a new, genetically engineered version of a hormone that stimulates blood cell production. Erythropoietin, either alone or in combination with hydroxyurea, did not appear to benefit patients with the disease.
Although only three patients received hydroxurea, each had been hospitalized several times a year for severe, painful crises before taking the drug.
"All three of them had virtual cessation of pain crises," said H. Franklin Bunn, director of hematology research at Brigham and Women's Hospital in Boston and the report's senior author. He said that other researchers have told him they are having similar success with hydroxyurea. He called the results "the most gratifying experience I've had as a physician."
One of the patients in the study, Mamie Jones, 42, of Dorchester, Mass., said in an interview that before taking hydroxyurea, she had been hospitalized between four and 12 times a year for severe pain in her legs, chest or back caused by sickle cell anemia. She said that since she began taking the drug 15 months ago, she has not had to enter the hospital.
"I've been feeling great," she said. "Once in a while, I have a little pain, but nothing I can't deal with at home."
Sickle cell anemia is an inherited disorder, afflicting three of every 2,000 American blacks, in which each cell has two abnormal copies of the gene bearing the instructions for making adult hemoglobin. They cause the cell to make a defective form of hemoglobin molecules that, under certain conditions, will link, or polymerize, into long chains. The hemoglobin polymers cause the cell to change into the sickle shape that cannot flow smoothly through capillaries. As a result the blood cells jam, clogging circulation and causing painful tissue damage.
The search for an effective treatment has long focused on finding a drug that would increase production of fetal hemoglobin. It protects against sickling by inserting itself between molecules of abnormal hemoglobin, blocking polymerization.
Patients receiving the drug in the new study had increased concentrations of fetal hemoglobin in their blood cells. Their cells were more resistant to sickling and breakage, and survived in the circulation up to twice as long as cells from the same patients studied before the treatment began.
Hydroxyurea has significant side effects. It blocks the synthesis of DNA, a normal step in cell division, and for this reason is used for cancer chemotherapy. It can reduce white blood cell and platelet counts. The dosage must be individually adjusted.
"If a physician doesn't have experience with this drug and experience with treating sickle cell patients, there can be difficulties," Bunn said.