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AML is the most common form of acute leukemia, striking about 12,000 adults a year in the United States. Treatment usually involves chemotherapy to achieve a first remission, but the best subsequent therapy to prolong disease-free survival has been unclear, although the researchers say the results of this latest review could lead to a new standard of care.
"First complete remission does not mean you are cured. It doesn't mean that you have eradicated every last cancer cell; in fact, we know you haven't," said review author John Koreth of the Dana Farber Cancer Institute in Boston. "If we stop therapy, then almost invariably the disease will relapse, and you die from a relapse of the leukemia."
The next step is to achieve a cure and, for that, several treatment options exist. One is more chemotherapy; another is an autologous cell transplant, which uses the patient's own bone marrow cells. The third option is to use compatible donor stem cells in what is called an allogeneic transplant, Koreth said.
"The question has been which of these treatments is the best," he said. The report appears in the June 10 issue of the Journal of the American Medical Association.
Currently, treatment decisions are often based on risk of relapse, a determination made through chromosome analysis, called cytogenetic analysis. Depending on the results, patients are put into good-, intermediate- and poor-risk groups for the likelihood of survival at three and five years, Koreth said.
The traditional consensus has been to use chemotherapy or autologous transplants with patients in good risk. "For patients with poor-risk acute myeloid leukemia, the consensus has been they should all go to donor transplantation. For people in the biggest group, intermediate risk, there has really been no consensus," he said.
To determine which treatment is best for which patient, Koreth's team analyzed data from 24 clinical trials. They looked at the relapse-free survival and the benefit of allogeneic stem-cell transplantation vs. nonallogeneic stem-cell transplantation, plus chemotherapy for patients who had good, intermediate or poor survival risk.
The researchers found that patients with poor- and intermediate-risk AML who received allogeneic stem cell transplants -- the donor stem cells -- in first clinical remission were more likely to survive and less likely to suffer a relapse over the long term than patients given alternative therapies.
"For all comers, there is a statistically meaningful survival benefit to getting a donor transplant," Koreth said.
People in the poor-risk group had a survival advantage, which is consistent with current practice, he noted.
Without a donor transplant, the survival range for those in the poor-risk group is 15% to 20% at five years. With a donor transplant, the chance of disease-free survival at five years is about 33%.
For patients in the intermediate-risk group, a donor transplant was also clearly associated with improved survival -- of around 40%, Koreth said. This could become the new standard of care for these patients, he said.
"This is obviously not a home run yet," Koreth said. "We need better treatments, but for what we have today, this [donor cell transplantation] is a better treatment than the alternative."
Dr. Marshall A. Lichtman, professor of medicine, biochemistry and biophysics at the University of Rochester Medical Center, described the study as a very thoughtful analysis of a complex problem.
"It does reinforce that the cytogenetic abnormality in the leukemic cells of a patient are a singularly important factor, but not the only factor, in determining the therapeutic approach," Lichtman said.
"As the authors emphasize, their study gives the therapist an evidence-based perspective on the use of allogeneic stem-cell transplantation in the patient with acute myelogenous leukemia who has entered a chemotherapy-induced remission, always recognizing that these group data may require modification to satisfy the special circumstances of an individual patient," he said.
"If I find out I have acute myeloid leukemia, I want them to do my cytogenetics and tailor the therapy to fit me and my disease," Kamen said. "This article confirms that."
SOURCES: John Koreth, M.B.B.S., Ph.D., Dana Farber Cancer Institute, Boston; Marshall A. Lichtman, M.D., professor, medicine, biochemistry and biophysics, University of Rochester Medical Center, New York; Barton A. Kamen, M.D., Ph.D., chief medical officer, Leukemia & Lymphoma Society, White Plains, N.Y.; June 10, 2009, Journal of the American Medical Association
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