Dec. 12, 2001 Using a tag-team approach, researchers believe they may be able to increase survival for patients with multiple myeloma. In a multicenter study led by Dr. David Maloney at the Fred Hutchinson Cancer Research Center in Seattle, it was shown that by combining standard high-dose therapy and autologous stem-cell "rescue" with a procedure known as "mini-transplantation" from a sibling, that transplant-related toxicities could be reduced and survival increased for people diagnosed with multiple myeloma. Preliminary results from the study will be presented at the 43rd annual meeting of the American Society of Hematology in Orlando, Fla.
The phase II study involved 41 patients, ages 39-71, who had advanced-stage multiple myeloma. All patients had previously undergone chemotherapy to treat their disease. Now, more than four hundred days after undergoing treatment, 85 percent of these people are still surviving, leading researchers to believe that this two-step treatment option has real potential as a cure for this disease. The lead patients are now three years out from transplant without evidence of disease. "Harnessing the power of the donor immune system to eradicate cancer with a lower toxicity is exciting and promising," says Maloney. The process, called allogeneic immunotherapy has also been successfully used for the treatment of patients with leukemia, lymphoma and a solid tumor called renal cell cancer."
The first step in the two-step process is high-dose chemotherapy followed by a transplant using the patient's own stem cells to reduce the disease burden. Typically, patients undergoing high-dose chemotherapy often experience a number of complications that can be life threatening. The second step, one to three months later, is the mini-transplant procedure, during which the patient undergoes low-dose radiation followed by an infusion of stem cells from a matched brother or sister.
The concept of mini-transplantation was developed in preclinical studies at the Fred Hutchinson Cancer Research Center in a the group led by Dr. Rainer Storb, head of transplantation biology at the Hutchinson Center.
Maloney and colleagues believe that by separating the high-dose conditioning regimen from the immunotherapeutic effect of mini-transplantation, there is a decrease in death due to the transplant related complications. Mini-transplantation establishes an initial tolerance between the donor cells and the patient's own tissues, a phenomenon called "mixed hematopoietic chimerism." Later, the new immune system of the donor replaces the patient's bone marrow. In the process, the donor immune system attacks the malignant myeloma cells, through a graft-versus-myeloma effect.
For the patients, the treatment experience in step two is dramatically different from step one, requiring less hospitalization with most undergoing the procedure in an outpatient setting. Clinic visits are two to three times a week the first month and once or twice a week for the duration of their recovery period. Also, treatment-related toxicities are mild to moderate. The low-dose radiation does not cause the usual severe side effects associated with a high-dose transplant such as nausea, vomiting or diarrhea, and patients do not lose their hair. More significantly, blood counts never drop below levels the body needs to fight infections and stop bleeding.
Multiple myeloma is a cancer of the bone marrow that most often affects older adults. Depending on the stage of the disease at diagnosis, survival time ranges between three and five years. Upon diagnosis, the first goal for treatment is to relieve symptoms. There is no known cure to date.
Over the years, bone-marrow transplantation has been proven as a successful treatment for leukemia, lymphoma and a number of other blood and genetic disorders. While long-term survival after transplantation has increased significantly over the years and many people survive to live healthy and productive lives, a number of people are unable to tolerate the rigors of the therapy, especially people over age 50. It is known that the toxic effects of conventional stem-cell transplants are a major problem for older patients as well as younger patents with medical problems. Mini-transplantation offers options for these people.
Fred Hutchinson Cancer Research Center is recognized as a leader in cancer research. Its objective is to eliminate cancer as a cause of human suffering and death. The Hutchinson Center conducts research of the highest standards to improve prevention, diagnosis and treatment of cancer and related diseases. The Center's clinical research is focused on improving therapies for adults and children through the conduct of clinical trials, many involving bone-marrow and stem-cell transplantation.
Researchers from four leading cancer centers, nationally and internationally, participated in this study, including the Fred Hutchinson Cancer Research Center, Veterans Administration Medical Center in Seattle, the City of Hope Medical Center in Duarte, Cal.; Stanford University Medical Center, and the University of Leipzig in Germany.
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