Drug holds promise as an alternative for sickle cell patients unable to tolerate standard treatment

November 17, 2003

(WASHINGTON, DC, November 17, 2003) -- A new drug may offer relief from sickle cell symptoms for patients who do not respond to the current standard of care, according to the December 1, 2003, issue of Blood, the official journal of the American Society of Hematology.

Sickle cell disease is an inherited disorder that causes patients' bone marrow to produce red blood cells with defective hemoglobin, which in turn causes red blood cells to become sickle-shaped. These irregular cells have difficulty passing through blood vessels, causing many symptoms, including excruciating pain episodes, recurrent pneumonias, and strokes.

"The standard treatment for sickle cell is the drug hydroxyurea. Hydroxyurea reactivates fetal hemoglobin, and increased fetal hemoglobin production is known to decrease the complications of sickle cell disease," said Yogen Saunthararajah, M.D., of the University of Illinois at Chicago, the lead author of the study. "Not all patients respond to treatment with hydroxyurea, prompting our team to investigate whether the antimetabolite drug decitabine could be used effectively in place of hydroxyurea for these patients."

To be eligible for this study, patients had to be 18 years of age or older and have sickle cell disease which was symptomatic. In addition, patients had to be either resistant to or intolerant of hydroxyurea. Between November 2001 and February 2002, eight patients were enrolled in the study. All patients had multiple clinically significant complications of sickle cell disease. Three patients had been on hydroxyurea for more than one year and failed to demonstrate a significant increase in fetal hemoglobin or decreased symptoms, and the remaining patients were forced to discontinue use of hydroxyurea due to complications. Decitabine was administered at relatively low doses of 0.2 mg/kg one to three times per week in two six-week cycles, with a two-week interval between cycles. The drug was administered subcutaneously in the thigh or upper arm.

Fetal hemoglobin levels and a number of other markers of disease activity improved in all patients, including those who had not responded to previous treatment with hydroxyurea. Patients tolerated decitabine well, with the only significant toxicity being neutropenia.

According to Dr. Saunthararajah, "Decitabine induces the production of fetal hemoglobin probably through a different mechanism than hydroxyurea. These results are exciting as patients who do not respond to hydroxyurea need alternative therapies that can increase the quality and quantity of their lives. Further studies with decitabine should be performed to demonstrate if this agent, administered over prolonged periods of time, can improve the quality of life for patients with sickle cell disease."

Richard T. Maziarz, M.D., Director of the Center for Hematologic Malignancies at Oregon Health & Science University, notes, "Great progress has been made in the care of patients with blood disorders over the past two decades by defining the molecular basis of their disease and developing therapies that circumvent these abnormalities. Unfortunately, there still are many disorders, like sickle cell disease, for which limited treatment options still remain. The observation that decitabine may provide a therapeutic option for those patients with sickle cell disease that are resistant or intolerant of hydroxyurea is noteworthy. However, further study is necessary to better define how or if this agent can be used with long term benefit and safety. Additionally, the effect of decitabine, using the dosage schedule examined, on the non-red cell blood counts suggests that further dose finding studies will be required."

In the United States, there are between 4,000 and 5,000 children born each year at risk for sickle cell disease. Across the world, it is estimated that more than 125,000 new cases are diagnosed annually.

This work was supported in part by SuperGen, Inc., the Illinois Department of Health/UIC Sickle Cell Center, the Sickle Cell Disease Association of America, and Public Health Services grants from the National Institutes of Health.

To receive a copy of the study or to arrange an interview with Yogen Saunthararajah, M.D., please contact Aislinn Raedy at (202) 776-0544 or araedy@hematology.org.
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The American Society of Hematology is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.

Blood, the official journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers twice per month, available in print and online at www.bloodjournal.org.

American Society of Hematology

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