RESEARCH AREA

The Hemoglobinopathy Center

Transfusion Medicine
In order to decrease iron overload, I initiated a red cell pheresis program designed to test the hypothesis that red cell pheresis can delay or prevent the need for Desferal therapy in chronically transfused sickle cell patients. Preliminary data suggests chelation may be unnecessary in the pheresis group.

I have a long-standing research interest in the etiology and treatment of alloimmunization. In a study published in the New England Journal of Medicine, I showed that phenotypic genetic differences account for majority of alloantibodies in sickle cell disease. I recently published a study showing that a genetic difference between the donor and recipient is the cause of transfusion reactions in Asian thalassemia patients. Our first national trial evaluating phenotypically matched units for chronically transfused patients will be published in the September issue of the journal Transfusion. These studies revealed an increased occurrence in autoantibodies in patients which appears secondary to immune deregulation caused by alloantibodies.

Sickle Cell Anemia
We have coordinated several multicenter trials in sickle cell disease. Last June, the New England Journal of Medicine published our first paper on acute chest syndrome, a study in which bronchoscopy was utilized to define the etiology of lung injury. The next three manuscripts are on Chlamydia and mycoplasma in sickle cell disease, and the effect of transfusion on oxygenation. Our multicenter trial of decompression coring for avascular necrosis is progressing well. This study evaluates treatments to prevent progression of avascular necrosis to hip replacement.

Sickle cell brain studies have become a major focus of our program. These studies utilize neurocognitve testing and functional imaging. We want to define the extent of brain ischemia in MRI negative sickle cell patients and design a clinical trial to test neuroprotective agents.

Thalassemia
Three studies in thalassemia are currently in progress. The largest is a collaborative study involving centers in Oakland, London, Toronto, and Sri Lanka. The study’s goal is to define the natural history of E thalassemia and its response to combination chemotherapy (butyrate hydroxurea and erythpoietin). Two new trials looking at early treatment of osteoporosis with biphosphonates and treatment of hepatic C with combination therapy have been initiated.