This 12-month study will evaluate the safety and effectiveness of hydroxyurea in treating
beta-thalassemia, a type of anemia caused by defective hemoglobin (the oxygen-carrying
pigment in blood). Hemoglobin is composed of two protein chains-alpha globin chains and
beta globin chains; patients with beta-thalassemia do not make beta globin. Patients often
require frequent red blood cell transfusions. This leads to iron overload, which, in turn,
requires iron chelation therapy (removal of iron from the blood).
Some drugs, including hydroxyurea, can stimulate production of a third type of protein chain
called gamma chains. In the womb, the fetus makes this type of protein instead of beta
globin. It is not until after birth, when the fetus no longer produces gamma globin that
the beta globin deficiency becomes apparent. Gamma chain synthesis improves hemoglobin and
red blood cell production, correcting the anemia. This study will determine if and at what
dose hydroxyurea treatment reduces patients' need for red blood cell transfusions and
whether certain factors might predict which patients are likely benefit from this treatment.
Patients 15 years and older with moderately severe beta-thalassemia may be eligible for this
study. Participants will take hydroxyurea daily at a dose calculated according to the
patient's body size. Blood will be drawn weekly to measure blood cell and platelet counts.
The drug dosage may be increased after 12 weeks of treatment and again after 24 weeks if the
white cell and platelet counts remain stable. Patients who respond dramatically to
treatment may continue to receive hydroxyurea for up to 3 years.
Individuals with homozygous beta thalassemia are either severely anemic or dependent on
blood transfusion to sustain life. Deficient synthesis of the beta chain leads to
imbalanced chain synthesis with an excess of alpha globin. This alpha globin precipitates,
causing ineffective erythropoiesis and shortened red cell survival. Hydroxyurea is a
cell-cycle specific agent that blocks DNA synthesis by inhibiting ribonuclease reductase,
the enzyme that converts ribonucleotides to deoxyribonucleotides. Administration of
hydroxyurea to primates and more than 300 patients with sickle cell anemia has been
frequently, but not invariably associated with a substantial increase in synthesis of gamma
globin. In patients with homozygous beta-thalassemia, enhanced gamma globin synthesis could
partially compensate for the deficient synthesis of beta globin rendering chain synthesis
more balanced and reducing the relative excess of alpha chains. The purpose of this
protocol is to test the hypothesis that chronic daily low dose administration of hydroxyurea
will enhance gamma globin synthesis, increase red cell production and partially or
substantially correct the anemia in patients with homozygous beta-thalassemia. The effect
of treatment will be monitored by serial determination of the hemoglobin and hematocrit.
The relationship between response to therapy and the specific beta-globin mutation(s) will
also be analyzed. This study will therefore examine a cohort of patients not previously
treated with hydroxyurea.
Beta-Thalassemia Intermedia patients.
Steady-state Hb values greater than 6.5gm/dl (unrelated to transfusion)
Males and females.
Patients greater than 15 years of age.
Patients who are transfusion-requiring but not dependent will be offered the opportunity
Stable renal and hepatic function
Willingness to use appropriate birth control measures.
Ability to give informed consent.
No beta-thalassemia major.
No blood transfusion requirement greater than 1 unit every 2 months over the last 12
No patients with WBC less than 4000/micrograms.
No one with a platelet count less than 150,000/micrograms.
No evidence of active viral infective, including viral hepatitis.
No abnormal liver function test (ALT or AST greater than 2.5 x normal).
No abnormal renal function test (creatinine greater 1.5 mg/dl).
No HIV positive blood test.