Nonmyeloablative approaches to the treatment of sickle hemoglobinopathies

Significant advances in the field of sickle cell disease (SCD) in recent years have contributed to improving the life expectancy and symptoms of patients with this disease. These health care improvements include the implementation of infectious prophylaxis in children and the modulation of hemoglobin F production with chemotherapy. In spite of these advances, SCD continues to be associated with significant morbidity and mortality. Although standard allogeneic bone marrow transplantation can cure SCD and can halt the progression to end-organ damage, this treatment is associated with greater risk of toxicity and death in older patients and in those with evidence of severe end-organ damage. Nonmyeloablative conditioning regimens based on the use of purine analogs can induce sufficient immunosuppression to allow engraftment after allogeneic stem cell transplantation, resulting in less toxicity than standard conditioning regimens. We describe a clinical trial using a nonmyeloablative chemotherapy conditioning regimen followed by related allogeneic peripheral blood stem cell transplantation that represents a novel approach to the treatment of severe SCD in young adults. This study may afford chimeric engraftment resulting in the resolution or amelioration of disease-related symptoms and in the cessation of progression to organ failure.