A History of Cord Blood Banking and Transplantation

My interest in blood stem cells and cord blood dates back to my fellowship in Pediatric Hematology/Oncology at Duke. During my fellowship, I worked on the development of novel antileukemia drugs based on analogs of purine metabolism and treated a teenage patient with refractory T-cell acute lymphoblastic leukemia with a novel antileukemia drug, 20-deoxycoformycin, an inhibiter of adenosine deaminase. During 5-day course of therapy, his leukemia converted from a T-lymphoid to a myeloid phenotype before our eyes [1]. I subsequently established a cell line from these leukemic cells, DU-528 and, ultimately, proved that this leukemia arose from a common lymphoid-myeloid progenitor cell [2], which then led me to the study of hematopoietic stem and progenitor cells. Hal Broxmeyer, who would go on to become a pioneer in the use of cord blood as a source of donor cells for bone marrow reconstitution, mentored me as I studied normal and malignant hematopoietic stem cells isolated from bone marrow, fetal liver, and umbilical cord blood. In the clinic, I cared for children with leukemias and blood dyscrasias, including a young boy named Matthew Farrow from Salisbury, NC, with Fanconi anemia (FA) and evolving bone marrow failure. This genetic disease, which arises from a mutation in genes that encode the enzymes responsible for DNA repair, is associated with a host of serious medical and developmental problems. The prognosis for Matthew’s condition was stark: most children with Fanconi anemia died of bone marrow failure or leukemia in the first decade of life, unless treated with a bone marrow transplant from a human leukocyte antigen (HLA)-matched donor. Matthew did not have a living related matched donor, but when his mother became pregnant with another baby, the unborn fetus was tested to see if she was affected with FA and, if not, was a match for Matthew. An amniocentesis was performed and samples were sent to Arlynn Auerbach, a renowned researcher at the Rockefeller University in New York who was the first to describe the mutations responsible for Fanconi anemia and who established the FA patient registry [3]. Dr. Auerbach confirmed that Matthew’s sibling was healthy and an HLA identical match.What happened next was a remarkable convergence of insight, dedication, and cooperative innovation in this emerging therapeutic area. At that time, the only potentially curative therapy for Fanconi anemia was a bone marrow transplant from a healthy matched related donor. However, at the Memorial Sloan Kettering Cancer Center (MSKCC), a team led by Ted Boyse, Judy Bard, and Hal Broxmeyer was exploring the potential uses of cord blood in transplantation and cell therapy. Although cord blood hitherto was routinely discarded as medical waste, the trio had formed a company, Biocyte, to develop therapeutic applications for cord blood and obtained a patent for the freezing and banking of cord blood for future use. Dr. Broxmeyer’s research had confirmed that cord blood was enriched for highly proliferative hematopoietic cell progenitors—even more so than bone marrow—and hypothesized that cord blood could serve as a substitute donor for bone marrow transplantation [4]. Meanwhile, Dr. Boyse had performed preliminary testing of the concept in mice, although biological differences limited the usefulness of animal-model testing, Dr. Auerbach, who had been working with Broxmeyer on some of the biological aspects of patients with Fanconi anemia who converted from one disease phenotype to another, was aware of a mutual interest. The group had been hoping to pilot their therapeutic approach in human patients, but their plans had recently been put on hold when a family interested in participating turned out not to be candidates for the procedure after all—in their case, the potential donor sibling was found to also have Fanconi anemia. It was at this point that Dr. Auerbach approached us to ask if we might be interested in using Matthew’s sister’s cord blood as the donor for his transplant. We talked with Matthew’s parents, who talked with Matthew, then a young 5 years of age, to determine whether he thought the transplant was a good idea. It was Matthew who ultimately made the final decision, which was yes. Gordon Douglas, an obstetrician from New York Hospital traveled to and stayed in Salisbury, NC, for several weeks to attend the delivery of Matthew’s sister so that he could collect her cord blood. Shortly after the birth of Matthew’s sister, the cord blood was collected into a wide mouthed bottle containing heparin to prevent clotting. HLA typing was confirmed at Duke, and the cord blood was taken to Hal Broxmeyer’s laboratory at MSKCC and cryopreserved, after addition of dimethyl sulfoxide but without other processing, JOANNE KURTZBERG, M.D.