LAUSR

During the second part of the 20th century, Dr E. Donnall Thomas worked on refining bone marrow transplantations using a dog model at the Fred Hutchinson Cancer Research Center (“The Hutch”) in Seattle, WA. His previous transplants had shown short-term success when bone marrow from identical twins was used. In 1979, the first patient with leukemia was successfully treated with a transplant from an unrelated donor using new immunosuppressant drugs. Critical to the success of these experiments was the transfusion support from Bloodworks Northwest (formerly known as “Puget Sound Blood Center”). The blood center, located just down the street from the Hutch in Seattle's First Hill neighborhood, provided platelets to help patients over their critical thrombocytopenic periods during transplantation. Thomas mentored Dr Sherrill Slichter, an up-and-coming platelet transfusion investigator. However, their relationship was not always harmonious. Slichter describes in her memoirs how Thomas commented on one of her research proposals: “Did your parents speak English at home?” Of course, Slichter, being the usual relentless and persistent force of nature, took those comments as a challenge and succeeded by receiving funding from the National Institute of Health to work on the improvement of platelet storage. Critical to Thomas' success was also the optimization of immunosuppressive regimes. Dr Rainer Storb, a junior physician and Fulbright Scholar from Germany, joined Thomas' team in 1965. Thomas gave Storb the freedom to pursue his interest in improving immunosuppressive therapies for allogeneic bone marrow transplants. Storb is well-known today for his work on non-myeloablative stem cell transplantation. In 1990, Thomas received the Nobel Prize for Physiology for his bone marrow transplant research. The paper highlighted in this Association for the Advancement of Blood & Biotherapies' (AABB's) 75th Anniversary Series must be viewed in this historical context. At the time, platelet transfusions had been established but had frequently led to refractoriness due to alloimmunization. Alloimmunization to donor antigens specifically involves human leukocyte antigens (HLA). In HLA-alloimmunized individuals, the recipients have antibodies against “foreign” HLA and do not respond to platelets from donors with the corresponding HLA antigens. These patients require HLA-matched platelet donations, a time-consuming and arduous procedure involving donors, the clinical care team, the transfusion service, and the blood provider. Prolonged periods of severe, untreated thrombocytopenia pose a clear risk for potentially fatal bleeding in patients. Thomas and Storb had used dog models to establish and refine allogeneic bone marrow transplantation regimens because (a) like humans, dogs have remarkable phenotypic diversity, (b) dogs have a well-mixed gene pool, and (c) dogs can develop hematological diseases, including non-Hodgkin lymphoma. Also, the dog model allows for transfusion of antigen-mismatched platelets, which is considered unethical in healthy humans. Because of all these advantages, Slichter began to develop her platelet alloimmunization research in dog models. For this study published in 1988, Slichter joined Storb and tried different immunosuppressive regimes previously used by Storb for bone marrow transplantation. They also tested how to reduce the immunogenicity of the platelet storage bag (involving a whopping 200 and Received: 27 June 2022 Accepted: 27 June 2022