High-dose chemotherapy and bone marrow transplant (HDC/BMT), also high-dose chemotherapy with autologous bone marrow transplant (HDC/ABMT or just ABMT), was an ineffective treatment regimen for metastatic breast cancer, and later high-risk breast cancer, that was considered promising during the 1980s and 1990s. With an overall idea that more is better, this process involved taking cells from the person's bone marrow to store in a lab, then to give such high doses of chemotherapy drugs that the remaining bone marrow was destroyed, and then to inject the cells taken earlier back into the body as replacement. It was ultimately determined to be no more effective than normal treatment, and to have significantly higher side effects, including treatment-related death. From its birth in the 1980s to its denouncement in the late 1990s, HDC/BMT transformed clinical practice, activist-driven legislation on healthcare insurance coverage, public health policy and drove a two-decade long period of entrepreneurial oncology. It also gave rise to one of the most serious cases of research misconduct of the 20th century.
History The idea for high-dose chemotherapy (HDC) with autologous bone marrow transplant (ABMT) originated in the 1950s as a leukemia treatment, when E. Donnall Thomas had shown that bone marrow could be harvested from a person and transplanted into the same or another person. It was promoted as a treatment for advanced breast cancer starting in the 1980s. The treatment of high-dose chemotherapy with autologous bone marrow transplant had serious, lasting, and sometimes deadly side effects for the patient, including cardiac toxicity, sepsis, pulmonary failure, and nephrotoxicity, among others. Chronic consequences of the treatment included development of leukemias and lymphomas and heightened vulnerability to infections soon after the transplant. Randomized clinical trials reported treatment-mortality rates from 0% to 7% for women who received the HDC/BMT treatment, versus no such deaths within the control groups that received the typical chemotherapy regimen. In HDC, the bone marrow transplantation was used to maximise chemotherapeutic dosage. By harvesting and freezing bone marrow, then implanting the marrow after HDC, doctors were theoretically able to break through the frontier of toxicity, the so-called "red ceiling". Early proponents of the technique were George Canellos and Emil Frei of the Dana–Farber Cancer Institute, and William Peters, whom Frei had recruited to the institute in 1982. Howard Skipper and Frank Schabel demonstrated efficacy in mouse models for megadose therapy in 1983. Frei and Peters developed the Solid Tumor Autologous Marrow Program (STAMP) regimen. Researchers in the National Cancer Institute (NCI) did not believe that the treatment would be effective and were wary of the consequences of this treatment. For example, George Canellos, one of the original members of the NCI, had noticed that a long-term side effect of megadose chemotherapy regimens was myelodysplasia, a condition that tended to progress to leukemia. During the early stages of the STAMP clinical trial, the first patients were those who were hopeless cases—women with advanced, metastatic breast cancer that had already received, and did not respond to, existing treatments. However, about halfway through the trial, a previously untreated woman with metastatic breast cancer enrolled in the STAMP program, and many of Peters's colleagues began to take notice. The results of her treatment were unprecedented—her tumor and metastatic deposits had shrunk significantly. From then until the end of this preliminary clinical trial, Peters had transplanted and treated more cases and also obtained significant remissions similar to that of this woman's. They then believed that STAMP produced more durable remissions than those by conventional chemotherapy, and so Peters left to set up a randomized clinical trial at Duke University.
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