The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, relatively low lymphocyte and hematopoietic stem and progenitor cell dose is a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit before transplantation. Ex vivo expansion has the potential to increase the number of lymphocytes, committed progenitors and long-term repopulating hematopoietic stem cells. Increasing the numbers of lymphocytes and committed progenitor cells will address the issue of delayed hematopoietic recovery after umbilical cord blood transplantation. Increasing the hematopoietic stem cell content will improve the availability of adequately sized and matched cord blood units for transplantation. It may also eliminate the need for dual umbilical cord blood transplantation for those without an adequately sized single umbilical cord blood graft. The second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late-phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.
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