What’s New for Umbilical Cord Blood
Transplantation?

Once again this year, the clinical use of umbilical cord blood (UCB) as a source of hematopoietic stem cell graft commands an education program dedicated to this subject. The Stem Cell Transplantation (Cord Blood Transplants) Education Session was presented yesterday and will repeat again today at 7:30 a.m. In this session, three prominent scientists/clinicians collaborate to bring you a full cover of different topics that are critical for the widespread use of UCB in clinical transplantation.

Dr. Nelson J. Chao (Duke University) will discuss patient outcomes in different transplantation settings focusing on the use of UCB with both myeloablative and non-myeloablative preparative regimens and discuss how close we are to using UCB in adult patients.

Dr. Stephen G. Emerson (University of Pennsylvania) will update us on the potential ex vivo expansion of UCB stem cells using novel genetic approaches and will assess the clinical experience with the use of such expanded grafts.

Finally, Dr. Kenneth I. Weinberg (Children’s Hospital of Los Angeles) will evaluate the immune reconstitution following UCB transplantation and will compare the development of competent T cell function in recipients of UCB-derived versus other sources of stem cells. These three speakers and the topics of discussion will undoubtedly leave you with a fair volume of new and exciting information about what is new in the area of UCB transplantation.

Dr. Chao will begin with a comprehensive comparison of the outcomes of UCB transplantation in different myeloablative preparative regimens updated from 861 unrelated transplants. Collectively, these studies indicate that age of the recipient is an important factor in determining success, with younger patients generally doing better. Under these settings, it appears as if UCB contains enough hematopoietic stem cells to engraft successfully in adult patients and may be associated with less severe acute GVHD, even in HLA-disparate matching. The main advantage concluded from transplants conducted with a non-myeloablative regimen, although the number of patients examined on these studies was smaller, appears to be the superior maintenance of peripheral niches required for T cell development compared to myeloabla-tive treatments, and hence, robust myeloid and T cell recovery in these patients. The decreased damage caused by nonmyeloablative treatments relative to myeloabla-tive regimens is probably responsible for the efficient expansion of T cells in the periphery and enhanced reconstitution.

Dr. Emerson will begin by reiterating the so far disappointing results of ex vivo expansion of UCB-derived stem cells in conventional cytokine-supplemented cultures due to either failure in achieving true expansion of stem cells or to the absence of conclusive testing of these preparations in clinical trial settings. Dr. Emerson will conclude with an overview of some more promising approaches for the expansion of UCB stem cells that utilize novel genetic molecules such as the activation of Notch-1 and WntILEF-1 pathways. The most promising approach to date is that of focusing on HoxB4 and its role in self-renewal. While we are on the subject of HoxB4, we should mention that more presentations on the topic covering very recent data on the use of HoxB4 in expansion protocols will be discussed extensively in the Simultaneous Oral Session, “Stem Cell Self Renewal,” on Monday at 11:00 a.m.

Dr. Weinberg will give us an overview of the relationship between immune reconstitution in stem cell transplantation patients and the source of stem cells in the graft. A primary factor contributing to the delayed immunorecon-stitution in cord blood transplantation patients is the small number of progenitors contained in UCB. Whether the “younger” age of UCB stem cells is a factor in their reduced potential for lymphocyte development is unknown. Also unknown are the effects of the placenta, as the site of the hematopoietic microenvironment of UCB, on the proliferative and differentiation capacity of these cells. All of these factors, in addition to possible strategies that may overcome the clinical impediments observed with UCB transplantation, will be discussed in a very exciting overview of the immunology of cord blood. This session will be an informative mix of both clinical and basic science data.