The specific aims of this proposal are (1) to cooperate with other clinical centers and a coordinating center to provide patients for a study of the use of hydroxyurea (HU) in sickle cell anemia (S/S): (2) to assess the variables affecting the degree of response to HU therapy; the maximum effective non-toxic dose; individual patient response in terms of F-reticulocytes, F-cells and Hb F/F-cell; and factors mitigating this response among patients. (3) To see whether prolonged administration of HU is practical, patient acceptable and free of serious side effects and long-term risks if carefully monitored. (4) To see if treatment with HU, which acts by increasing F-cells and F/F-cell, can, by so doing, improve the quality of life of S/S patients by reducing the frequency and severity of painful vaso-occlusive crises. To this end about four patients will be recruited from this center and prepared for HU therapy according to protocols to be agreed between the investigators. Once selected, they will be prescribed HU at a dose of 15 mg/kg/day and investigated by blood test twice weekly for changes in F-reticulocytes etc. or toxic effects. If no toxicity is noted the dose will be increased by 5 mg/kg/day at suitable intervals until the maximum response is obtained short of toxicity. Patients will be followed over a 21/2 year period to assess the overall response to this therapy and its feasibility in a larger group of patients. Throughout the study this center will collaborate closely with the coordinating center in the investigation of patients for toxic effects and efficacy by mailing appropriate blood samples expediciously and adjusting dosages in accordance with agreed protocols.
