AUTHOR=Bhalla Nishka , Bhargav Anjali , Yadav Sandeep Kumar , Singh Aloukick Kumar 

TITLE=Allogeneic hematopoietic stem cell transplantation to cure sickle cell disease: A review

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1036939

DOI=10.3389/fmed.2023.1036939

ISSN=2296-858X

ABSTRACT=Sickle cell disease (SCD) had first been mentioned in the literature a century ago. Advancement in the molecular basis of pathophysiology of the disease opens the door for various therapeutic options. Though the life-extending treatments are available for SCD patients, allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is the only option as of yet. A major obstacle before HSCT to cure SCD patients is the availability of donors. Matched sibling donors are available for a small percentage of patients. To expand the donor pool, different contrasting approaches of allogeneic-HSCT like T cell replete and deplete have been tested. None of those tested approaches have been without the risk of GvHD and graft rejection. Other limitations such as transplantation-related infections and organ dysfunction caused due to the harsh conditioning regimen needs to be addressed on a priority basis. In this review, we will discuss available allogeneic HSCT approaches to cure SCD, as well as recent advancements to make the approach safer. The center of the interest is to use of megadose T cell-depleted bone marrow in conjugation with donor-derived CD8 veto T cells to achieve engraftment and tolerance across MHC barriers, under reduced intensity conditioning (RIC). This approach is in phase 1/2 clinical trial at MD Anderson Cancer Centre and is open to patients with hemoglobinopathies.