ABSTRACT
The first successful human allogeneic hematopoietic stem cell transplantations (HSCT) were
performed in children with congenital immunodeficiencies in 1968 (1-3). Since then, bone
marrow transplantation (BMT) has been proven to cure or provide survival advantage for
several malignant and nonmalignant diseases. However, several challenges limit the success
rate and ability to utilize BMT. Only about 30% of potential HSCT recipients have a suitably
human leukocyte antigen (HLA)–matched related donor. Unrelated donor (URD) transplants
are associated with higher transplant-related mortality (TRM) due to graft failure,
opportunistic infections, and graft-versus-host disease (GVHD). URD searches are time
consuming with median search times reported in the range of four months (4-8). Donor
attrition is another challenge: about 30% of suitably matched URD, even when identified, are
not available when needed for a variety of reasons (8). As a result, only about 50% of the
initiated URD searches are successful in terms of identifying an HLA-matched donor who is
still motivated and available (8). Hence, an unknown number of patients succumb to their
primary disease while awaiting a suitable graft (9). These limitations led to incentives
for newer strategies, including the search for alternative sources of hematopoietic stem
cells (HSC).