Stem Cell / Bone Marrow Transplant - Historical Perspective (1950s-1960s)

After studies demonstrated that bone marrow could be transplanted and engraft in animals that had received high-dose radiation therapy, scientists began to evaluate stem cell / bone marrow transplants as a method of effectively treating human malignancies. While the initial attempts in 1957 did not cure patients, these attempts showed that bone marrow could be given intravenously to human patients without significant side effects. In 1959, three published reports described successful engraftment of marrow cells in humans after infusion that followed irradiation. However after initial remission, all patients experienced disease recurrence, suggesting that radiation therapy alone is insufficient to cure underlying disease.

These early studies indicated that bone marrow transplantation could be successfully performed, temporarily resulting in remission of the patient’s underlying disease. However, the lack of appropriate technology for human leukocyte antigen (HLA) typing, inadequate supportive care, and the use of total body irradiation alone probably contributed to the lack of success of the transplantation. The modern era of hematopoietic stem cell / bone marrow transplantation began at the end of the 1960s. In November 1968, an infant with severe combined immunodeficiency (SCIDS) underwent a bone marrow transplant and was cured of his immunodeficiency. In March 1969, a patient with leukemia received a graft from a matched sibling. Subsequent studies of patients whose severe aplastic anemia or leukemia were treated with bone marrow transplants from matched sibling demonstrated that transplanted marrow cells could successfully engraft, and that this engraftment resulted in prolonged remission after appropriate regimens consisting of chemotherapy and radiation. After these initial reports of curative transplantation, investigators attempted to apply this therapeutic approach to a variety of diseases and at points earlier in the treatment course. However, many problems with venous access and complications such as graft-vs-host disease (GvHD), infections, organ toxicity and disease recurrence remained significant barriers to the success of transplantation. In addition, severe side effects occurred in recipients of grafts from HLA-mismatched family members.

After bone marrow transplant, patients must undergo frequent blood sampling and blood product transfusion, and need intravenous medications, and total parenteral nutrition, fluids and electrolytes; these processes and the administration of these compounds require long-term venous access. During the early stages of stem cell / bone marrow transplant development, long-term venous access was difficult to maintain. However, specialized venous access devices have since been developed to overcome this problem.