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).