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
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.
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.
Three studies in thalassemia are currently in progress. The largest is
a collaborative study involving centers in Oakland, London, Toronto, and
Sri Lanka. The studys 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.