Optimizing the right time to start sickle cell therapies

Area of Science:

• Hematology
• Genetics
• Pharmacology

Background:

• Sickle cell disease (SCD) is a complex genetic disorder causing hemolysis and vaso-occlusion with diverse complications.
• Newborn screening allows early SCD identification, but optimal timing for disease-modifying therapies (DMTs) is debated.

Purpose of the Study:

• To review how genetic, clinical, and phenotypic factors influence the timing of DMT initiation in SCD.
• To emphasize the evolving trend towards earlier and personalized SCD treatment strategies.

Main Methods:

• Literature review of genetic and clinical risk factors impacting SCD treatment timing.
• Analysis of current and emerging DMTs, including hydroxyurea, L-glutamine, crizanlizumab, voxelotor, stem cell transplantation, and gene therapies.

Main Results:

• Early hydroxyurea initiation is supported for severe SCD genotypes but faces underutilization.
• A growing number of therapies exist, necessitating individualized treatment decisions.
• Phenotypic variability and risk stratification are key to optimizing intervention timing.

Conclusions:

• A shift from reactive to proactive care models is needed for SCD management.
• Multiagent approaches and biomarker-driven strategies may enhance outcomes.
• Optimizing DMT timing improves quality of life and long-term survival in SCD.