Umbilical cord blood transplantation supported by third-party donor cells: rationale, results, and applications.

Low incidence of graft-versus-host disease provides the major rational for pursuing umbilical cord blood (UCB) stem cell transplantation (SCT). Considerable evidence also suggests a lower rate of recurrence after UCB SCT than after transplantation from adult donors. Recent advances in understanding of the human fetal immune development provide a rational underpinning for these clinical outcomes. The fetal immune system is geared toward maintaining tolerance to foreign antigens, particularly to the maternal antigens to which it is exposed throughout gestation. To this purpose it is dominated by a unique population of peripheral T regulatory cells that actively maintain tolerance. This and other features of the UCB lymphoid system explains the low incidence of graft-versus-host disease and superior outcomes of UCB SCT with noninherited maternal antigen-matched grafts. At the same time, highly sensitized maternal microchimeric cells are frequently detected in UCB and likely contribute to superior graft-versus-leukemia effects and low rates of disease recurrence in inherited paternal antigen-matched UCB recipients. However, historically erratic and slow hematopoietic recovery after UCB SCT leads to increased early morbidity and mortality, excessive hospitalization, and increased costs. This has held up the widespread utilization of UCB SCT in adults. Here we summarize recent data on UCB SCT with an emphasis on studies of co-infusion of adult CD34 selected hematopoietic stem cells with UCB SCT. This procedure, through transient engraftment of adult hematopoietic stem cells, largely overcomes the problem of delayed engraftment. It also results in predictable engraftment of a UCB with the desired characteristics. We also briefly discuss unresolved issues and possible future applications of this technology.