Hematopoietic stem cell transplant for lysosomal storage diseases

Hematopoietic stem cell transplantation (HSCT) for lysosomal storage diseases (LSD) has been performed for over 20 years. In that time, many advances have been made in understanding the unique pathophysiology of the various LSDs. We have also made advances in HSCT, particularly in the use of umbilical cord blood as a stem cell source. The goal of HSCT has always been to correct the deficient lysosomal enzyme through the engraftment of enzyme replete donor cells that include cells of the hematopoietic system and it's derivatives (i.e. brain microglia). In those LSDs that are accompanied by some form of neuro-degeneration as part of their phenotype, one of the primary endpoints of performing HSCT is to slow or arrest the neurodegenerative process. As a general rule, earlier HSCT leads to improved outcomes since irreversible organ and tissue damage has had less time to occur. Mostly through trial and error we have learned which LSDs respond best to HSCT and which have shown minimal improvement after HSCT. Due to the rare nature of LSDs, this learning process is not complete. Even after two decades of performing HSCT for LSDs, many experiences are still being published as case reports. In recent years, the advent of enzyme replacement therapy for several of the LSDs offers new avenues for treatments that can be complemented by HSCT. In this review, we discuss what is currently known of HSCT related outcomes in the treatment of LSDs.