Bone Marrow Transplant - Historical Perspective (1970s-Present)

In the late 1970s, bone marrow transplantation techniques were expanded from allogeneic sibling driven transplantation to autologous transplantation. This method was developed in response to the findings that escalating doses of chemotherapy resulted in the destruction of increasing numbers of tumor cells. In addition, studies showed that the incidence of regimen-related toxicities associated with autologous stem cell / bone marrow transplant was lower than that associated with allogeneic transplantation. This reduced incidence of toxicity allowed stem cell / bone marrow transplants to be extended to patients with high-risk solid tumors and lymphomas. During the past decade, the hematopoietic stem cells used to support high- dose chemotherapy and radiotherapy regimens have been derived from peripheral blood rather than from bone marrow. The use of peripheral blood stem cells results in blood-forming cells that more rapidly reconstitute the blood counts than the use of bone marrow stem cells.

As transplantation outcomes improved, the donor pool was expanded to include alternative donors because matched sibling donors were available for only about 20 percent of potential transplant recipients. In 1986, the National Marrow Donor Program (NMDP) was established to facilitate transplantation of marrow from donors who were unrelated to potential recipients. Even with the NMDP registry, unrelated donors are not available for all patients.

In the early 1990s, reports that hematopoietic stem cells could be isolated from umbilical cord blood led to research in the use of new stem cells from this newly identified source. Initial studies demonstrated that patients receiving cord blood transplants have a lower incidence of GvHD. However, because the number of stem cells in cord blood is small, this technique was largely limited to young children. During the same era, researchers demonstrated that the therapeutic effects of allogeneic transplant rely not only on radio-chemotherapy but also on an immune effect called graft-versus-leukemia effect. In the late 1990’s to present, increasing success has been reported using mismatch family donor (heplo-identical) grafts. This expands the availability of transplantation to almost all patients. While graft-versus-leukemia effect was largely attributed to a subset of white blood cells called T-cells in the 1990’s, research conducted in 2000’s demonstrated that another subset of white cells called NK cells also contribute significantly to antileukemia effect. Therefore, donor typing has extended beyond HLA typing to include NK cell typing.