Although sickle cell disease (SCD) is probably the most common severe genetic disorder in the world, there are still only 3 therapeutic interventions that have been convincingly shown to alter the natural history of the condition in clinical trials: penicillin prophylaxis (prevention of invasive pneumococcal disease), hydroxyurea (reduction of acute complications, primary stroke prevention), and regular blood transfusion (primary stroke prevention). Although there are other treatments that are undoubtedly beneficial, including vaccination, analgesia, intermittent blood transfusion for symptomatic anemia, and hematopoietic stem cell transplantation, the treatment options in SCD are currently very limited.
Clinical management has lagged behind molecular discoveries. It was initially considered a form of rheumatism, and the treatment of acute pain in the 1920s, with rest and analgesia, was remarkably similar to its treatment today.1 In addition, it was believed that SCD was nearly always lethal in childhood until the 1970s when specialist care started to develop, particularly in the United States with the Sickle Cell Anemia Control Act.
Clinical care and research for SCD have historically been underfunded relative to other rare inherited and life-threatening conditions such as cystic fibrosis (CF).2,3 In a study examining funding per affected individual, funding was 11.4-fold greater for CF than SCD and included 3.5-fold higher National Institutes of Health (NIH) funding and 440-fold higher national foundation funding. NIH career development awards were similar for the 2 diseases despite that there are nearly 3-fold more individuals affected by SCD in the United States. Recent emphasis on SCD by the Department of Health and Human Services4 and the American Society of Hematology is anticipated to change the landscape of research and access to care in the coming years.
To date, 3 randomized controlled trials have had a major impact on the management and prognosis of sickle cell anemia (SCA) in high-income countries: the Prophylaxis With Oral Penicillin in Children With Sickle Cell Anemia (PROPS) study showing that penicillin prophylaxis reduces morbidity and mortality from invasive pneumococcal disease at least until the age of 5 years,5 the Multicenter Study of Hydroxyurea (MSH) showing the reduction of painful episodes and acute chest syndrome by hydroxyurea in adults,6 and the Stroke Prevention Trial in Sickle Cell Anemia (STOP) showing evidence for primary stroke prevention using transcranial Doppler measurements and long-term blood transfusion.7 Further studies have demonstrated extended benefits of hydroxyurea, including in primary stroke prevention,8 and most importantly have shown its effectiveness in sub-Saharan Africa.9 It is now widely accepted that specialist care should include neonatal screening, prophylaxis against infection, primary stroke prevention, and widespread use of hydroxyurea. However, even with these interventions, median life expectancy is still reduced by 20 or 30 years in SCA,10 and this standard of care in only available in high-income countries. This improvement in life expectancy has mostly been achieved through the application of basic supportive medical care and has ...