New Strategies in the Treatment of the Thalassemias

Abstract

In addition to the severe beta thalassemias, hematologists have begun to recognize the more severe forms of alpha thalassemia, namely hemoglobin (Hb) H disease and Hb H/Hb Constant Spring, as well as the beta compound heterozygote, beta thalassemia/HbE. Clinically, variably severe anemia becomes apparent in the first year accompanied by occasionally massive expansion of erythropoiesis. The most anemic patients require regular red blood cell transfusions to avoid death from cardiac failure. However, the inevitable iron accumulation leads to dysfunction, primarily involving the heart, liver, and endocrine system; thus, regularly transfused patients require iron chelation. A major discovery was that allogeneic bone marrow (stem cell) transplantation in severely affected subjects with both alpha and beta thalassemia could result in cure. Current work deals with specific complications, such as iron overload and endocrine, cardiopulmonary, thrombophilic, and osteopenic problems. The thalassemias are likely to benefit in the future from specific gene therapy. There are also important advances in genetic counseling based on results of early fetal diagnosis.

Treatment of hepatitis C in patients with thalassemia

“…3,4 Hemopoietic stem cell transplantation is a widely performed procedure which offers the possibility of definitively curing thalassemia. 5 However, with the dramatically improved survival of patients with thalassemia major, care providers face new clinical scenarios and new challenges associated with the longer life and aging of these patients.…”

Randomized trial of two different conditioning regimens for bone marrow transplantation in thalassemia – the role of busulfan pharmacokinetics in determining outcome

“…Lucarelli et al have shown that for children who have no hepatomegaly or fibrosis in the liver and have been adequately chelated (Class I), an event-free survival (EFS) of 92% can be achieved with transplantation, but for children who have been inadequately managed before transplant with all three risk factors (Class III), the transplant-related complications and rejection are high and the EFS is only 60%. 1,2 Rejection is a major problem in BMT for thalassemia, with rates varying from 11 to 55% in different series of BMT for thalassemia. 3,4 Busulfan (Bu) and cyclophosphamide (Cy) are the two agents used most commonly for conditioning in BMT for thalassemia and of these two, Bu is considered to be the main agent for myeloablation.…”

Understanding Beta-Thalassemia with Focus on the Indian Subcontinent and the Middle East

“…Since it was developed by the Pesaro group in 1981 there have been more than a 1000 patients with transplantations with a thalassemia-free survival rate of 68% [71]. Thus far, allogeneic bone marrow transplantation seems to provide a definitive cure of this disease.…”