Umbilical Cord Transplantation: State of the Art 2010

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• From Biological Waste to Medical Miracle
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October 24, 2008 marked the 20th anniversary of the first umbilical cord blood (UCB) transplant performed in Paris in a child with Fanconi anemia. Since that time, an estimated 20,000 transplants have been performed with about half in adults. Despite considerable early skepticism, UCB is now routinely and widely used. This edition of Seminars in Hematology was devoted to UCB because of the substantial accomplishments made in this field over the past two decades. Not only has UCB become an accepted source of hematopoietic stem cells (HSC) for transplantation, new uses as lymphoid effector cells and non-hematopoietic stem cells promise to expand its application well beyond that of classic blood and marrow transplant.

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From Biological Waste to Medical Miracle 

This issue is the compilation of the latest advances in the field. In the various articles, key leaders have provided their personal “take” on the current state of the science. While the overarching goal of this issue is to provide a review of what is known about UCB today, it is hoped it will also assist the clinician in making the typical day-to-day decisions on the appropriate use of UCB. Not surprisingly, no one HSC source addresses all the obstacles—but, if nothing else, UCB has made transplant more widely available.

In the first article, Eliane Gluckman and I summarize the early history of UCB transplantation, which we hope sets the stage for the second generation of studies being initiated today. During the first generation, we were collectively able to establish the cell dose threshold associated with reliable engraftment. In addition, we found an interaction between human leukocyte antigen (HLA) match and cell dose, such that the deleterious impact of HLA mismatch could be at least partially compensated for by increasing cell dose. In the second article, Andromachi Scaradavou summarizes the effects of HLA and cell dose and proposes an evidence-based approach to UCB unit selection. Next, Mitchell Cairo and Paul Szabolcs discuss what is known today about the pattern and pace of immune recovery and the risks of opportunistic infections during this recovery period. By understanding the risk factors for delayed recovery, perhaps new interventions can be developed to “bridge” this period of immune compromise. In the fourth article, Margaret MacMillan, Mark Walters, and Eliane Gluckman summarize UCB transplant outcomes that are currently observed in patients with bone marrow failure or hemoglobinopathy. While a heterogeneous population of patients, poor engraftment is a recurrent theme in such recipients of unrelated donor UCB. In contrast, high success rates in terms of engraftment and survival are consistently observed in the setting of HLA-matched sibling UCB, particularly for patients with Fanconi anemia and hemoglobinopathy. Newer approaches for securing engraftment in these patient populations are now being explored. After this, Mary Eapen and I describe current transplant outcomes in children with acute leukemia, comparing the results observed in recipients of unrelated donor marrow and those receiving UCB. Despite HLA mismatch, it is increasingly clear that, for children with acute leukemia, UCB is as good as 8/8 allele-level HLA-matched marrow, the “gold standard.” In the absence of randomized controlled trials, these are the most compelling data to date supporting UCB as a first-line therapy. In the next article, Rachel Hough and Vanderson Rocha also summarize current transplant outcomes in children with acute leukemia, but this time comparing the results observed in recipients of haploidentical related marrow and UCB. Importantly, while risks may vary between HSC sources, the overall leukemia-free survival rates are similar. These results suggest that haploidentical related marrow is an appropriate alternative, especially at centers focused on the management of complications after haploidentical bone marrow transplantation. In the seventh article, Vinod Prasad and Joanne Kurtzberg present UCB transplant outcomes in children with mucopolysaccharidoses. Survival rates and neuropsychological evaluations after transplant have been very promising. Similarly, in the next article, Paul Orchard and Jakub Tolar summarize UCB transplant outcomes in children and young adults with leukodystrophy with comparisons to results after bone marrow transplantation. As with various marrow failure syndromes and hemoglobinopathy, engraftment remains an obstacle and new strategies are being evaluated to overcome this barrier. Angela Smith and K. Scott Baker next summarize UCB transplant outcomes in children with immunodeficiency syndromes, describing promising results similar to those reported for such children transplanted with marrow. Next, Claudio Brunstein and Mary Laughlin summarize UCB transplant outcomes in adults with acute leukemia and other malignant disorders, treated either with a myeloablative or a nonmyeloablative therapy. Work to date is very promising in both settings. All told, these results provide the proof of concept that UCB is useful, particularly in those situations when an 8/8 allele HLA matched unrelated adult volunteer is not available. Finally, Hal Broxmeyer, who provided the most compelling in vitro and in vivo murine data that laid the foundation for the past clinical trials, ends with predictions of where the field will go.

It is hoped that this issue of Seminars of Hematology not only accurately reviews the current state of knowledge but also helps us imagine where the UCB field might be 20 years from now. For me, it has been an amazing journey that began with a phone call from a concerned grandmother who desperately hoped that UCB might give her 4-year-old grandson suffering from juvenile myelomonocytic leukemia a better chance. We simply cannot underestimate the power of our patients and their families who compel us to try new things that sometimes revolutionize the practice of medicine.