The very first bone marrow transplants came in the form of oral delivery of healthy marrow to patients with diseases of the blood. This treatment was not particularly successful, but physicians had the right idea: donor marrow cells, when administered, may find their way into the cell-producing cavities of bone.
Eventually, laboratory experimenters were able to demonstrate that mice with damaged bone marrow could be restored to health if injected with healthy marrow from other mice. Physicians soon began to speculate whether such a procedure could be carried out in humans (allogeneic transplantation).
In 1956, the first successful human bone marrow transplant was performed by Dr. E. Donnall Thomas of Cooperstown, New York. Thomas reported that total body irradiation followed by infusion of marrow from an identical twin could result in complete remission of leukemia.
Though Thomas’s findings were exciting, marrow transplants of this sort were not performed on a large scale until Jean Dausset, a French medical researcher, made a critical discovery about the human immune system in 1958. Human histocompatibility antigens, Dausset described, are proteins on the surface of most cells in the body. The immune system uses these proteins to identify which cells belong in the body, and which do not, so that it may defend itself accordingly. The better the antigen match between donor and recipient, therefore, the less likely it is that T cells (immune system cells) of the donated marrow will react against the patient’s body. Thus, doctors began to focus on the extent to which these HLA-antigens need to match in order to complete a successful transplant.
Up until now, the only successful human marrow transplants had been those between identical twins, for these transplants guarantee perfect HLA compatibility between donor and recipient. In 1968, however, enough was known about the HLA system for a transplant between siblings to occur. Dr. Robert A. Good performed the first successful transplant of this sort in 1968 at the University of Minnesota: the recipient was a four-month-old boy who had inherited severe combined immunodeficiency syndrome (“bubble boy syndrome”) and the donor was his eight-year-old HLA-matched sister. The disease had previously killed 11 male children in the boy’s family.
Expanding knowledge of the HLA-system allowed a team at Memorial Sloan-Kettering Cancer Center in New York City to perform the first unrelated bone marrow transplant in 1973 on a five-year-old patient suffering from sever combined immunodeficiency syndrome. The matched donor was found in Denmark through the Blood Bank at Rigshospitalet in Copenhagen. The patient received multiple infusions of marrow, and after the seventh transplant, engraftment was achieved and hematologic function became normal.
The increasing success of bone marrow transplantation prompted the medical community to create a large database of HLA-typed volunteers, so that patients without matching donors in their families could have an alternative option for transplant. This expansion was triggered by the family of Laura Graves, a young patient from Fort Collins, Colorado who was diagnosed with acute leukemia in 1979. The patient’s family was referred to the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle for treatment of the disease.
Unfortunately, no one in Graves’s family was a good match, so the staff at FHCRC began to search the registries of typed platelet donors. Remarkably, a match was found within the staff at the center, and Ms. Graves became the first leukemia patient to be treated with an unrelated bone marrow transplant. The cells engrafted without complication, and the patient went home after 100 days of hospitalization and careful monitoring. Graves survived for two more years before passing away due to relapse of her leukemia.
The patient’s family, inspired by the previous events, helped to establish individual registries of HLA-typed people in Milwaukee, Saint Paul, Seattle, and Iowa City. Staff organization got its first batch of donors by approaching previously HLA-typed platelet donors and asking them if they would donate marrow as well. Before long, the families of other patients who were in need of a good HLA match began organizing similar efforts in their own communities. Because tissue typing is so expensive, however, these donor drives were small and slow-progressing. Occasionally, matches were found, but it soon became obvious that a coordinated, nationwide effort was necessary to have a large impact on these patients.
A group which consisted of physicians, families, and Graves’s family worked tirelessly to achieve the goal of a national donor registry, realizing that in order to succeed, they needed congressional support. In 1984, Congress passed the National Organ Transplant Act, which included language to evaluate unrelated marrow transplantation, and possible plans to establish a national registry.
This was accomplished with the hard work of several individuals:
Two years after the passing of the National Organ Transplant act, Congress approved the formation of a national registry, and The National Bone Marrow Donor Registry (NBMDR) began operations in July 1986. The organization was supported by The American Red Cross, and housed at its Saint Paul Regional Blood Services (where Dr. McCullough was medical director). By the end of 1986, 39 donor centers in 22 states had joined the NBMDR.
In 1988, the Organ Transplants Amendment Act reauthorized the NBMDR by directing establishment of a national registry. In June of that year, the NBMDR changed its name to the National Marrow Donor Program (NMDP).
The NMDP became a separate non-profit organization in 1990, taking over administration of the federal contract from the American Red Cross in Saint Paul and establishing new headquarters across the Mississippi River in Minneapolis. The Transplant Amendments Act of 1990 further defined and expanded the role of the NMDP in the medical community, writing into law the network of centers, addressing the need for diversity, and coordinating all registries and establishing a system for patient advocacy.
The first donor was identified in December of 1987: Diane Walters of Milwaukee, Wisconsin, was a perfect match for Brooke Ward, a six-year-old girl in Raleigh, North Carolina who had been diagnosed with acute lymphoblastic leukemia three years earlier.
Around the time of the scheduled transplant, a terrible winter storm descended on the Milwaukee airport. Only the bravery of a private pilot in a small airplane made it possible to deliver the marrow in time. The transplant was performed at the Fred Hutchinson Cancer Research Center in Seattle, and Brooke’s life was extended for an additional two years.
Dr. Thomas, who had performed the first human bone marrow transplant in 1956, wins the 1990 Nobel Prize in Physiology or Medicine for his pioneering work in the area of organ and cell transplantation. From the early to mid-1970’s, Dr. Thomas performed over 100 transplants for patients with aplastic anemia and leukemia who had HLA-compatible siblings. A brief autobiography of Thomas can be found here.
1991: The NMDP establishes the Office of Patient Advocacy in order to:
1992: As the number of patients and donors rapidly increased, it was clear that new technology was needed to organize the registry’s data. In 1992, the NMDP introduced the Search, Tracking and Registry (STAR) System in order to:
Because HLA tissue traits are inherited, it became increasingly apparent that a patient’s best chance of finding a good match was with a brother or sister. The next best match, however, was usually someone of the same race or ethnicity. Thus, increasing donor diversity became a primary interest of the organization. In 1993, NMDP launched several new initiatives in various civic, community, corporate, and faith-based organizations in order to raise awareness of transplant technology and encourage people of varying backgrounds to join the registry.
The chances of obtaining a match increased for all racial and ethnic groups for the registry was growing rapidly, yet some patients were still unable to find a match due to rare HLA-typing. A pressing need still remains for more American Indian and Alaska Native, Black and African American, Hispanic and Latino, and Asian, Native Hawaiian and Other Pacific Islander donors.
By now, what was once considered an experimental procedure was now a widely used medical therapy for the treatment of numerous life threatening diseases.
Today, one may search for a matching marrow or blood donor form more than 6 million volunteer donors and more than 50,000 cord blood units on the NMDP Registry, the largest donor registry in the world. The NMDP network expands worldwide, with donor centers, transplant centers, and registries cooperating with NMDP in 35 countries. These extensive international connections result in approximately 40% of transplants receiving cells from an international donor, or an international patient receiving cells from a U.S. donor.
Each month, about 260 patients receive transplants through the NMDP. More than 25,000 transplants in total have occurred since the NMDP began operations in 1987.
Technology for transplantation continues to evolve, and the NMDP is ready to adapt to any changes that may occur. For example, new web-based software tools will soon allow transplant centers to search for patients even more quickly and efficiently, and DNA-based phenotyping will soon allow for selection of more closely matched donors.