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  • Print publication year: 2009
  • Online publication date: May 2010

32 - Stem Cell Transplantation

from SECTION EIGHT - NEW APPROACHES TO THE TREATMENT OF HEMOGLOBINOPATHIES AND THALASSEMIA

Summary

INTRODUCTION

Homozygous β thalassemia is characterized by absent or defective β-globin chain synthesis. This defect causes imbalance in chain production and accumulation of unstable α-globin tetramers in red blood cells or their precursors, leading to intramedullary destruction, apoptosis and hemolytic anemia (chapter 17). Regular transfusions and iron chelation has, in developed countries, transformed this disease from one fatal in infancy to a chronic disease with prolonged survival. Medical treatment is expensive and requires a complex multidisciplinary approach. In underdeveloped countries, where most patients reside, thalassemia remains fatal early in life because of poor access to modern medical treatment. Curing β thalassemia by hematopoietic cell transplantation, with the cost efficiencies inherent in this approach, is therefore an attractive option.

As in β thalassemia major, the objective of hematopoietic cell transplantation for sickle cell disease is to replace recipient erythropoiesis, or to reduce its clinical impact, by the expression of donor β-globin chains. The clinical benefit of this cellular replacement is the elimination, or significant amelioration, of the clinical complications caused by polymerized sickle hemoglobin. More than a decade ago, the initial clinical trials of hematopoietic cell transplantation for sickle cell disease indicated that the replacement of donor for sickle erythropoiesis might eliminate not only the hematological manifestations of the underlying disorder, but also stabilize and even reduce the organ damage caused by recurrent vasoocclusion occlusion and hemolysis. As in malignant disorders, there is utility in assigning a risk-based approach to applying transplantation for sickle cell disease.

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