Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for many diseases, such as hematologic malignancies, immune deficiency syndrome, and bone marrow (BM) failure. A human leukocyte antigen (HLA)-matched sibling donor is considered the best hematopoietic stem cell (HSC) donor; however, only approximately 30% of the patients can receive transplantation from an HLA-matched sibling donor. In the absence of such a donor, the search for an unrelated volunteer adult donor is currently performed and more than 14 million potential unrelated adult donors are registered with the unrelated-donor registries worldwide. However, the HLA-matched unrelated donors are found for only approximately 50% of the patients. Additionally, the search and procurement process for adult donors can take weeks or months; consequently, cord blood (CB) is becoming an increasingly attractive alternative to HLA-matched peripheral blood progenitor cells (PBPCs) or BM.

Since the CB was found to have sufficient progenitor cells for clinical hematopoietic reconstitution, researches showed that CB could be an alternative HSC source¹⁾. Thereafter, studies about collection, transportation, optimal cryopreservation of CB, and the viability of CB after thawing have been conducted. In 1988, the first CBT was performed in a patient with Fanconi anemia (FA)²⁾. Furthermore, in 1991, CB was successfully transplanted from an HLA-matched sibling to a child with acute lymphoblastic leukemia, and in 1993, CB was transplanted from an unrelated donor for the first time³⁾. CB, which was previously discarded after birth, has emerged as a valuable stem cell source and has led to remarkable progress in the field of allogeneic HSCT. The progress in the field of CBT aroused huge interest in the establishment and development of CB banks worldwide. These banks play an important role in the CBT process. In 1998, the Netcord group was created to establish good practices in CB storage, to facilitate donor search, to improve the quality of grafts, and to establish procedures for bank accreditation. At present, it is estimated that more than 400,000 CB units are available for transplantation in more than 100 CB banks in many countries.

Although CB contains one log fewer nucleated cells than BM or mobilized PBPC, it has a higher primitive HSC content and higher proliferative potential than either BM or mobilized PBPC. Therefore, CB may serve as a reliable source for HSCT despite the limited cell number.

The incidence of graft-versus-host disease (GVHD) is less than expected given the degree of HLA disparity in CBT. The exact reasons for the relatively low incidence of GVHD are unknown, but may result from the functional immaturity of infused lymphocytes, including decreased cytotoxicity, an altered cytokine profile, decreased HLA expression and increased regulatory T-cells⁴⁾. Despite a low incidence of GVHD in CBT, graft-versus-leukemia effect is preserved, which may be associated with natural killer cells in CB⁵⁾.

CB offers many advantages such as easy procurement with no risk for the donor, reduced risk of transmitting infections, and rapid availability of cryopreserved cell. CBT also permits transplantation in the absence of full HLA compatibility between donor and recipient. The disadvantages of CBT are the higher rate of graft failure, delayed hematopoietic recovery, the risk of genetic disorder transmission, and the inability to further obtain stem cells or donor lymphocyte infusion⁶⁾.

In 1996, the first CBT was attempted in a child with severe aplastic anemia, resulting in graft failure. A child with acute lymphoblastic leukemia achieved successful engraftment after CBT in 1998, but outcome was unsuccessful. Subsequently, a child with acute biphenotypic leukemia was successfully transplanted with CB and remained leukemia free¹¹⁾. However, CBT was not a realistic alternative to BM or PBPC transplantation in Korea until January 2003, when National Health Insurance started covering the cost of transplantation for children under the age of 16 years. Since then, the number of pediatric cases of CBT in Korea has increased dramatically. While 51 cases of CBT were performed for 7 years from 1996 to 2002, 49 cases were performed for one year of 2003. Many pediatric patients lacking a suitable donor can be transplanted and saved using CBT. In March 2004, the first successful double-unit CBT was accomplished in Korea for a 14-year-old girl with acute myeloid leukemia¹²⁾. In January 2009, the Korean National Health Insurance policy began to cover all CB recipients, including adults without an appropriate familial donor. From 2001 to 2011, 352 cases of CBT have been performed through the KoreaCORD, of which 157 patients underwent double-unit CBT. A recent study reported the outcomes of 236 patients who underwent CBT, performed from 1996 to 2003 in 13 transplantation centers in Korea. The results showed that acute leukemia was the most frequent primary disease. The median times to neutrophil and platelet recovery were 18 and 45 days, respectively. Grade 2-4 acute GVHD and chronic GVHD developed in 41.1% and 36.1% of the cases, respectively. The 5-year overall survival and event-free survival rates were 47.5% and 36.9%, respectively. Cytomegalovirus (CMV) disease developed in 45 patients (21%) and was an adverse factor for survival. These data suggest that careful management for CMV is important in Korean children, whose CMV seroprevalence exceeds 90%. Because an advanced disease status was found to be the most important risk factor for poor survival in the study, timely CBT is recommended when an appropriate BM or PBPC donor is not available¹³⁾.

Unrelated CB has emerged as an alternative allogeneic stem cell source. CB is readily available and provides suitable HLA-matched donors for patients who require allogeneic transplantation. CBT provides timely transplantation for patients with an unstable disease and reduces risk of GVHD without increased risk of relapse. In the clinical reports of CBT, the survival rates were comparable between transplants from CB and unrelated PBPC or BM in children with acute leukemia. The low incidence of chronic GVHD in CBT may benefit the quality of life of long-term survivors. Despite the limited cell dose in adult CBT, it is expected that reduced GVHD in CBT may reduce the TRM. Patients who do not have a matched sibling donor should simultaneously search for unrelated adult donors and CB. CBT is recommended, when the transplantation is urgent and a CB unit of nucleated cells of more than 2.0×10⁷/kg is available. With the rapid development in the field of CBT including biology of CB, clinical trials, and banking process of CB, future research will amplify the broad applications of CB and help greater numbers of future patients.