Pediatric sickle cell disease: past successes and future challenges

Area of Science:

• Hematology
• Pediatric Medicine
• Genetics

Background:

• Sickle cell disease (SCD) was historically fatal in childhood, but survival rates have significantly improved.
• Key advancements include newborn screening, penicillin prophylaxis, and transcranial Doppler (TCD) screening.
• Hydroxyurea (HU) is the primary oral medication for preventing SCD complications, with widespread use over the last two decades.

Observation:

• The NHLBI recommends HU for all HbSS patients from 9 months of age.
• The TWiTCH trial demonstrated HU as a viable alternative to transfusion therapy for stroke risk in high-risk patients.
• Hematopoietic stem cell transplant (HSCT) offers a cure but is limited by donor availability (less than 25% of patients).

Findings:

• Review summarizes early SCD pathophysiology research and improvements in supportive/preventive care.
• Highlights findings from the Silent Infarct Transfusion (SIT) Trial and TWiTCH trial.
• Discusses current investigations into alternative stem cell sources and gene therapy trials for SCD.

Implications:

• Improved survival rates for SCD patients into adulthood are achievable with current care strategies.
• Hydroxyurea therapy is a cornerstone in managing SCD, offering an alternative to transfusions for stroke prevention.
• Future research in HSCT and gene therapy holds promise for curative treatments for sickle cell disease.