of patient weight. This delayed recovery is associated with a high rate of treatment-related morbidity and mortality.

Research related to the improved clinical use of cord blood is being conducted in four general areas: (1) enhancement of cord blood engraftment, (2) improvements in immune reconstitution, (3) reduction in the rates of treatment-related mortality, and (4) augmentation of immune recognition of infectious agents and tumors. Further research is needed to better understand how cord blood may be used as a source of effector cells (i.e., performing a specific function in the immune system in response to a stimulus) outside the transplant setting. This includes the development of immune regulatory cells that might be useful in solid-organ transplant or for the treatment of autoimmune diseases. Cord blood could also be a source of pluripotent stem cells. Research suggests that these pluripotent stem cells, which are capable of differentiation into, for example, hepatocytes and neural progenitor cells, might be present in cord blood.

Research that may improve the effectiveness of cord blood transplantation for the treatment of a variety of conditions is ongoing, including: nonmyeloblative regimens; the use of ex vivo expansion to increase the numbers of HPCs and the development of new approaches to the acceleration of immune recovery; the use of multiple units in transplantation; the coinfusion of mesenchymal stem cells (MSC); and facilitation of the upregulation of homing receptors.

Cord Blood Transplantation After Nonmyeloablative Therapy

While cord blood as an alternative HPC source has several advantages, including rapid availability and lower risk of GVHD despite HLA-disparity, many older patients, or those with extensive prior therapy or serious co-morbidities, are unable to tolerate conventional myeloablative conditioning. In myeloblative conditioning, the patient’s healthy cells are destroyed along with the cancer cells during chemotherapy and total body irradiation. Therefore, reduced intensity or nonmyeloablative regimens are being investigated using either related or unrelated volunteer donors. However, given that many patients will not have a suitable adult donor, use of unrelated donor cord blood in combination with nonmyeloablative conditioning is being investigated in adults to further extend access to allogeneic transplant.

Several studies have been reported thus far. McSweeney et al. (2001) observed engraftment in 2 of 3 evaluable patients receiving fludarabine and total body irradiation 200 cGy. Chao et al. (2002) observed engraftment in 3 of 5 in patients receiving fludarabine cyclophosphamide and antithymocyte globulin. Barker et al. (2003) observed an incidence of sustained donor



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