The purpose of this study is to determine the natural history of hemoglobin E/B thalassemia (Hb E/B) and the clinical benefit of chemotherapy in its treatment. Hb E/B represents the most common form of thalassemia worldwide and is becoming the most common form in the United States. The most significant contributing factor for this increase in patients is the large influx of populations of Asian descent. A major deficiency in our knowledge about Hb/E/B is its natural history. As the search for alternative therapies to transfusion and chelation, which are either unobtainable or unsuccessful because of noncompliance, is made, it is essential to understand natural history in order to better determine who can best benefit from new therapies. Clearly many patients can benefit from alternative therapies. The most important new treatment is the manipulation of HbF. Pilot data from Toronto and Oakland demonstrate that selective patients may become transfusion independent with chemotherapy. The primary hypothesis of this study is that hydroxyurea alone or with sodium phenylbutyrate will result in a sustained increase of 2 grams or more of Hb.
The specific aims of the study: 1) To determine the clinical, phenotypic and genotypic picture of Hb E/B in order to understand its natural history and prognosis, 2) To determine the safety, compliance, and predictors of chemotherapy, and 3) To determine if, with chemotherapy, abnormalities in red cell membrane and survival are corrected. To answer the chemotherapy question, 30 eligible patients will be recruited. Initially low dose hydroxyurea at 7 mg/kg will be administered and then gradually increased every eight weeks until at least a 2 gm/dL total Hb increase has occurred. After one year of adequate therapy, sodium phenylbutyrate will be added at 10 gm/m2 for the following six months of therapy. During this period, hematologic, Hb F, red cell deformability, globin chain synthesis, and red cell survival will be monitored. The natural history study will be determined by an E/B-thalassemia consortium consisting of the Thalassemia Centers in Sri Lanka, Oakland, and Toronto. The 250 patients will be stratified by age and will undergo serial history, physical, and laboratory assessments. In summary, if this study is successful, it will change the approach to Hb E/B worldwide and result in improved quality of life and decreased mortality.
| Zhang, Liying; Magli, Alessandro; Catanese, Jacquelyn et al. (2011) Modulation of TGF-? signaling by endoglin in murine hemangioblast development and primitive hematopoiesis. Blood 118:88-97 |
| Singer, Sylvia T; Vichinsky, Elliott P; Larkin, Sandra et al. (2008) Hydroxycarbamide-induced changes in E/beta thalassemia red blood cells. Am J Hematol 83:842-5 |
