SEATTLE — June 1, 2001 — For people over 50 years of age with leukemia or some other potentially fatal blood cancers, there may now be the option of treatment with a donor stem cell transplant.
Researchers report that low-dose radiation therapy combined with immunosuppressive drugs allows donor stem-cell transplants in patients who cannot have conventional stem-cell transplants using donor stem cells or their own stem cells. Results from the study will be published in the June 1 issue of the journal Blood.
The toxic effects of conventional stem-cell transplants are a major problem for older patients or younger patents with medical problems. In the Fred Hutchinson Cancer Research Center-led study, researchers found that non-myeloablative stem-cell transplants, also known as mini-transplants, are a treatment option for these patients. The mini-transplant involved low doses of radiation, coupled with post-transplant immune suppression, to establish a stable state of tolerance between the donor cells and the patient's own tissues, a phenomenon called "mixed hematopoietic chimerism."
"We are deliberately reducing the total-body irradiation from the typical pre-bone marrow transplantation regimen doses of 1,200 to 1,500 centigray which is equivalent to being close to the epicenter of a nuclear bomb blast, to 200 centrigray," says Dr. Rainer Storb, senior investigator of the study, member of Fred Hutchinson Cancer Research Center, and professor of medicine at the University of Washington "The revolutionary part of the whole concept is that the cancer is eliminated through the donor T-cells rather than with high-dose chemo-radiation therapy."
In addition to the lower doses of chemotherapy and radiation the researchers attribute the positive responses to what is known as a graft-versus-tumor effect, a reaction where the donor T-cells fight and eradicate the host cells as well as the use of post-engraftment immunosuppression to control graft rejections and graft-versus-host-disease (GVHD).
Few of the patients required hospitalization, most undergoing the procedure in an outpatient setting, going into the clinic two to three times a week the first month and then once or twice a week for the duration of their recovery period. Also, the majority of the patients experienced mild to moderate treatment-related toxicities. For example, patients do not lose their hair. In contrast, conventional transplants in younger patients usually require greater than 30 days hospitalization.
"We are transplanting into the patient a new immune system that hopefully won't tolerate the cancer cells," says Dr. Peter McSweeney, lead investigator and first author on the study, former assistant member at the Hutchinson Center and now associate professor of medicine at the University of Colorado. "The ability to perform low-toxicity donor cell transplants in an outpatient setting may open the door to a new era of tumor immunotherapy in which donor immunity can be exploited, eventually for a wide range of cancers."
The study involved 45 patients treated between 1997 and 1999 who were ineligible for a conventional bone marrow or stem-cell transplant. The patients were of a median age of 56 years and had been diagnosed with acute and chronic leukemia, multiple myeloma, non-Hodgkin's lymphoma, and other diseases often treated with bone marrow transplantation. Eight patients with chronic leukemia entered a complete molecular remission, which is a state of no detectable cancer cells, and this suggests strongly that donor immune cells might eradicate these diseases. The patients were followed through their treatment and recovery period, an average of 417 days, and survival among the patients was approximately 66 percent.
Patients in the study were treated at the Hutchinson Center, University of Washington Medical Center, Veterans Affairs Medical Center in Seattle, the University of Leipzig in Germany, or Stanford University. By now, more than 300 patients have been treated with this procedure including more than 100 grafts from unrelated donors, and the number of collaborating institutions has been increased to ten.
Fred Hutchinson Cancer Research Center
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Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center, home of three Nobel laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, UW Medicine and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 40 nationwide. For more information, visit the center's website at www.fhcrc.org.