Hematopoietic Stem Cell Transplantation in Sickle Cell Disease: A Multidimentional Review

Area of Science:

• Hematology
• Transplantation Immunology
• Genetic Medicine

Background:

• Sickle cell disease (SCD) management has advanced with FDA-approved gene therapies, exagamglogene autotemcel and lovotibeglogene autotemcel.
• These novel treatments, however, are not universally accessible, necessitating exploration of alternative therapeutic strategies.
• Allogeneic hematopoietic stem cell transplant (HSCT) presents a curative option for SCD, but faces significant accessibility and safety hurdles.

Purpose of the Study:

• To review the current landscape of hematopoietic stem cell transplant (HSCT) for sickle cell disease (SCD).
• To discuss the indications, conditioning regimens, and challenges associated with donor availability for HSCT in SCD.
• To explore outcomes and the potential of alternative donor sources for HSCT in SCD patients.

Main Methods:

• Comprehensive literature review of hematopoietic stem cell transplant (HSCT) for sickle cell disease (SCD).
• Analysis of indications, donor matching criteria (including HLA-matched related donors), and conditioning protocols.
• Evaluation of post-transplant outcomes, complications, and strategies involving alternative donor sources.

Main Results:

• Hematopoietic stem cell transplant (HSCT) can eradicate sickle cell disease (SCD) symptoms.
• Availability of human leukocyte antigen (HLA)-matched related donors is a major limitation for HSCT in SCD.
• Patients with SCD face increased transplant complications due to disease-related pathophysiology.

Conclusions:

• Hematopoietic stem cell transplant (HSCT) remains a critical therapeutic option for sickle cell disease (SCD), despite challenges.
• Optimizing conditioning regimens and expanding the use of alternative donors are crucial for improving HSCT accessibility and success in SCD.
• Further research into HSCT protocols and donor sources is essential to overcome barriers to curative treatment for SCD.