Hydroxyurea for the Treatment of Patients With Sickle Cell Anemia
Hydroxyurea for the Treatment of Patients With Sickle Cell Anemia
A total of fifty severely affected patients with homozygous sickle cell disease or other
 sickling disorders (e.g. B negative or B positive Thalassemia/Sickle) who are greater than 18
 years of age will be eligible for treatment. Such patients must be able to tolerate an
 extensive period without blood transfusion and have relatively well preserved renal and
 hepatic function (creatinine less than 1.5 mg/dl and normal liver function test with
 exception of a mild elevation in transaminase). Evidence of severe sickle cell anemia will
 include recurrent pain crisis, chronic bone oain, evidence of aseptic necrosis with symptoms,
 and intractable leg ulcer, etc.

 On admission to the study, each patient will receive a complete history and physical
 examination. These data and standard laboratory evaluation, including a test for pregnancy if
 appropriate, will be adequate to ascertain whether any of the criteria for exclusion are
 present. Each patient must accept responsibility for for using an effective means of
 contraception. Patients who are found to be HIV positive will be excluded from the study....
Hydroxyurea is a cell-cycle specific agent that blocks DNA synthesis by inhibiting
 ribonucleotide reductase, the enzyme that converts ribonucleotides to deoxyribonucleotides.
 Hydroxyurea has been shown to induce the production of HbF, initially in non-human primates,
 and now in more than fifty patients with sickle cell anemia. The majority of patients with
 sickle cell disease respond to the drug with a more than two-fold increase in HbF levels; in
 some patients the percent of HbF exceeds 10 or 15 percent. It is estimated that levels of 20
 percent are required to substantially reduce the sickling propensity of red cells and to
 modulate disease severity. We propose now to treat several patients chronically with
 hydroxyurea to monitor the durability of the response, to examine for unanticipated long term
 sided effects and to determine hematological changes occurring longitudinally. Such patients
 will be candidates for protocols determining the ability of other agents to enhance HbF
 synthesis, especially in hydroxyurea non-responders. Finally, a series of in vitro studies
 are planned to attempt to develop predictors of response.
-  INCLUSION CRITERIA:

 A total of fifty severely affected patients with homozygous sickle cell disease or other
 sickling disorders (e.g., B negative or B positive Thalassemia/Sickle) who are greater than
 18 years of age will be eligible for treatment. Such patients must be able to tolerate an
 extensive period without blood transfusion and have relatively well preserved renal and
 hepatic function (creatinine less than 1.5 mg/dl and normal liver function test with
 exception of a mild elevation in transaminase). Evidence of severe sickle cell anemia will
 include recurrent pain crisis, chronic bone pain, evidence of aseptic necrosis with
 symptoms, and intractable leg ulcers, etc.

 EXCLUSION CRITERIA:

 Patients who are found to be HIV positive will be excluded from the study.