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The numbers of allogeneic stem cell transplants (SCTs) performed in the United States have increased steadily, from about 7,500 in 1994-1995 to over 13,500 in 2010-2011, in patients above the age of 20 years (1). Donor identification has been a constant challenge, and only 30% of patients who need allogeneic SCT have a matched sibling donor. The National Marrow Donor Program (NMDP) and its cooperative international registries have about 16 million volunteer donors. It is estimated that 75% of white patients, but only 16% of African Americans and other minority patients, will be able to find a suitably matched unrelated donor (MUD) and proceed to transplantation (2). Mismatched related (often haploidentical), cord blood (CB) or mismatched unrelated donors (MMUDs) with either peripheral blood (PB) or bone marrow (BM) graft sources are potential options for patients in need of a SCT but lacking a matched related donor (MRD) or unrelated donor.
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Using CB as the graft source provides many advantages; CB units are easy to collect with little or no risk to the mother or newborn. Cord blood units can be rapidly obtained for 80% to 95% of the patients 20 years and older across all races and in almost 100% of younger patients (2). This is particularly advantageous in cases where urgent transplant is mandated. Owing to rapid procurement of CB units, patients can receive CB transplantation (CBT) 4 or 5 weeks earlier than those receiving SCT with a MUD (3). Further, CBT is associated with low risk of infection transmission, requires less-stringent human leukocyte antigen (HLA)–matching criteria, and has relatively lower risk of graft-versus-host disease (GVHD) with preserved graft-versus-malignancy effects. However, it is associated with a greater risk of graft rejection, delayed engraftment, and delayed immune reconstitution, leading to heightened risk of infection or nonrelapse mortality (NRM) (4,5,6,7). Many of the adverse outcomes noted after CBT are attributed to the naïveté of CB T lymphocytes and the low numbers of total nucleated cells (TNCs) and CD34+ cells in the graft.
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CELL DOSE AND HUMAN LEUKOCYTE ANTIGEN MATCHING
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The outcomes of CBT depend on the impact of cell dose and the degree of HLA match (8). The TNC dose available for CBT is a fraction of what is typically used in the PB or BM setting. The median TNC dose obtained from a BM harvest is about 3 × 108 TNCs/kg; the granulocyte colony-stimulating factor (G-CSF)–mobilized PB can yield a median of 7 × 108 TNCs/kg (9). In contrast, about one-fourth of the CB units contain less than 0.25 × 108 TNCs/kg, and two-thirds of the units have between 0.25 × 108 to 1 × 108 TNCs/kg (8). The recommended minimum cell dose is typically 2 × 107 TNCs/kg for successful engraftment after ...