News Release

Drug may eliminate transfusions in patients with blood disorder

Peer-Reviewed Publication

American Society of Hematology

(WASHINGTON, DC, August 12, 2003) – The use of hydroxyurea may eliminate the need for future blood transfusions in children with beta-thalassemia major, an inherited blood disorder, according to a study published in the August 15th issue of Blood.

Beta-thalassemia is an inherited blood disorder that occurs when a person is unable to produce adequate levels of hemoglobin, the oxygen-carrying component of red blood cells. This genetic disorder probably arose about 6,000 years ago as a partial defense against malaria.

The most common treatment for severe forms of beta-thalassemia is red blood cell transfusions, which provide the patient with a temporary supply of healthy cells that function normally and supply the body with the needed oxygen. However, patients may experience severe complications from these transfusions, and in the developing world there are limited supplies of suitably tested red blood cells. Such complications lead researchers to look for alternative treatments to boost hemoglobin levels. Researchers from the Service d'Hematologie, Hopital Franz Fanon, in Blida, Algeria, hoped that administration of the drug hydroxyurea to patients with severe forms of beta-thalassemia would result in production of a useful form of hemoglobin called fetal hemoglobin. Hydroxyurea has previously been proven useful in treating sickle cell anemia.

In the study, seven transfusion-dependent beta-thalassemic children in Algeria were treated daily with hydroxyurea at the maximum levels. Of the seven patients, six had experienced transfusion-related complications, such as anaphylactic reactions, severe fever and chills, post-transfusional iron-metabolism problems and lack of venous access. Median follow-up was 19 months. Researchers targeted post-transfusional hemoglobin levels of 7 – 9 g/dl (grams per deciliter), since Algeria's blood supplies are limited. This range is under the normally recommended post-transfusional hemoglobin levels in countries with sufficient blood supplies.

The total fetal hemoglobin level increased in all patients, as early as the first month of treatment. Mean hemoglobin levels increased from 6.5 to 10.5 g/dl in two children with thalassemia intermedia, and from 4.5 ±0.9 to 7.0 ±0.8 g/dl in the five children with thalassemia major. The increase enabled five patients to stop undergoing transfusions. One patient needed two erythrocyte (red blood cell) concentrates after the fetal hemoglobin level fell during a pulmonary infection. Another patient underwent splenectomy (removal of the spleen) six months after beginning treatment to treat hypersplenism, a condition marked by excessive destruction of one or more kinds of blood cells in the spleen. That patient received two transfusions preoperatively and one perioperatively. None of the original seven patients have received additional transfusions. All of the children reported they felt better and more active.

Additionally, seven more patients who required regular transfusions have been treated with hydroxyurea. Although there have only been a few months of follow-up, two patients have discontinued transfusions, two patients have reduced the number of transfusions needed (one every two months instead of once a month), and three patients have continued treatment.

According to Stanley L. Schrier, M.D., President-Elect of the American Society of Hematology, "Those of us who care for thalassemics believe that their long range management will involve genetic manipulations that result in coordinated switching on of the deficient globin gene. However, pending that revolutionary therapy, interventions like the use of hydroxyurea to turn on gamma globin genes may have an important impact on the patients' quality of life."

Beta-thalassemia major, or Cooley's Anemia, is the most severe form of beta-thalassemia, requiring regular blood transfusions and extensive ongoing medical care. Patients with beta-thalassemia major require red blood cell transfusions every two to three weeks, which translates to as many as 52 pints of blood a year. These lifelong blood transfusions can lead to iron overload, which damages tissues in the liver, heart, endocrine organs, and joints. To prevent this, the iron accumulation must be treated with chelation therapy to prevent early death from organ failure. Some patients may undergo bone marrow transplantation with cells from a matched normal donor. However, this treatment is not available for all patients and entails significant risk.

According to the Cooley's Anemia Foundation, it is estimated that more than two million people in the United States carry the genetic trait for thalassemia. For this reason, the National Institutes of Health recommend that all U.S. citizens should be tested for the thalassemia trait.

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Blood, the Journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. All articles undergo rigorous peer review and are selected for publication on the basis of the originality and quality of the work described. As a special service to researchers and clinicians, accepted papers are made available online about three months ahead of print as "First Edition Papers." Blood is issued to Society members and other subscribers twice per month, available in print and online at www.bloodjournal.org.


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