title: Hydroxyurea and erythropoietin therapy in sickle cell anemia.
abstract: Hydroxyurea has been shown to increase fetal hemoglobin (Hb F) production in patients with sickle cell disease and therefore has the potential to alleviate both the hemolytic and vaso-occlusive manifestations of the disease. Preliminary evidence indicates that recombinant human erythropoietin (rhEpo) may also induce Hb F. Three sickle cell anemia patients were treated with escalating doses of intravenous rhEpo and, subsequently, with daily oral hydroxyurea. After the optimal hydroxyurea dose was attained, rhEpo was added again. Two additional patients were treated with hydroxyurea alone. Treatment with rhEp, either alone or in combination with hydroxyurea, had no significant effect on the percentage of F reticulocytes or F cells. In contrast, hydroxyurea treatment was associated with a 1.5-fold to sevenfold increase in F cells and a 2.3- to 27-fold increase in the percentage of Hb F. In the three patients whose response reached a plateau, hydroxyurea treatment was associated with lessened hemolysis, decreased serum bilirubin and lactate dehydrogenase levels, and prolonged 51chromium-labeled RBC survival. Hydroxyurea treatment also resulted in decreased numbers of irreversibly sickled cells and in decreased sickling at partial oxygen saturation, increased oxygen affinity, increased total RBC cation content, and diminished potassium:chloride co-transport. All five patients treated with hydroxyurea experienced a decrease in severity and frequency of painful sickle crises. This study confirms that hydroxyurea therapy increases Hb F production and provides objective evidence of a significant reduction in hemolytic rate and intracellular polymerization. In contrast, rhEpo, either alone or in combination with hydroxyurea, offered no measurable benefit. Based on these encouraging preliminary data, large-scale, controlled clinical trials are warranted to study the safety and efficacy of hydroxyurea in the treatment of sickle cell disease.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: M A
authors.initials: MA
authors.lastname: Goldberg
authors.forename: C
authors.initials: C
authors.lastname: Brugnara
authors.forename: G J
authors.initials: GJ
authors.lastname: Dover
authors.forename: L
authors.initials: L
authors.lastname: Schapira
authors.forename: L
authors.initials: L
authors.lastname: Lacroix
authors.forename: H F
authors.initials: HF
authors.lastname: Bunn
mesh_terms: D000284:Administration, Oral; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004912:Erythrocytes / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005319:Fetal Hemoglobin / Q000032:analysis; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D010108:Oxyhemoglobins / Q000378:metabolism; D011994:Recombinant Proteins; D012156:Reticulocytes / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D006451:Hemoglobin, Sickle; D010108:Oxyhemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D005319:Fetal Hemoglobin; D006918:Hydroxyurea