title: Single and combination drug therapy for fetal hemoglobin augmentation in hemoglobin E-beta 0-thalassemia: Considerations for treatment.
abstract: Patients with hemoglobin E (Hb E)-beta 0-thalassemia, one of the most common hemoglobinopathies worldwide, could benefit from drugs that increase fetal and total hemoglobin levels and thereby decrease the need for transfusions. The long-term clinical outcome of such therapy, its hematologic effects, and which patients are likely to benefit from treatment are unknown. Consequently, the use of such drugs for Hb E-beta 0-thalassemia is limited, and countries where resources for safe and regular transfusion are scarce cannot benefit from them. In a multicenter trial of 42 patients treated with hydroxyurea for two years, almost half the patients demonstrated a significant increase in steady-state hemoglobin level. Drug toxicity was minimal. Combined treatment of hydroxyurea with erythropoietin benefited selected patients, but the addition of sodium phenyl butyrate was ineffective. After 5 years of follow-up, a subset of patients remained off transfusions. Hydroxyurea should be considered for a subset of Hb E-beta 0-thalassemia patients.
authors.affiliation: Children's Hospital & Research Center at Oakland, 747 52nd St., Oakland, CA 94609, USA. tsinger@mail.cho.org
authors.forename: Sylvia T
authors.initials: ST
authors.lastname: Singer
authors.forename: Frans A
authors.initials: FA
authors.lastname: Kuypers
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Olivieri
authors.forename: David J
authors.initials: DJ
authors.lastname: Weatherall
authors.forename: Robert
authors.initials: R
authors.lastname: Mignacca
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Coates
authors.forename: Sally
authors.initials: S
authors.lastname: Davies
authors.forename: Nancy
authors.initials: N
authors.lastname: Sweeters
authors.forename: Elliott P
authors.initials: EP
authors.lastname: Vichinsky
mesh_terms: D001803:Blood Transfusion; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005147:Facial Bones / Q000000981:diagnostic imaging / Q000503:physiopathology; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D006446:Hemoglobin E / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use*; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000627:therapeutic use*; D011859:Radiography; D011994:Recombinant Proteins; D013156:Splenectomy; D013163:Splenomegaly; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery / Q000628:therapy
chemical_list: D010654:Phenylbutyrates; D011994:Recombinant Proteins; D004921:Erythropoietin; C075773:4-phenylbutyric acid; D005914:Globins; D006446:Hemoglobin E; D005319:Fetal Hemoglobin; D006918:Hydroxyurea