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Study identifies benefit of donor stem cell transplantation for adults with acute myeloid leukemia


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John Koreth, MBBS, DPhil

A stem cell transplant (SCT) from a compatible donor early in the course of disease is the best approach for the majority of young and middle-aged adult patients with acute myeloid leukemia (AML), according to a new analysis of two dozen clinical studies.

The findings of the study, published in the June 10 issue of the Journal of the American Medical Association by researchers at Dana-Farber Cancer Institute and other institutions, provide new guidelines for treatment of the disease. For all AML patients other than the minority with "good-risk" disease, SCT from a compatible donor significantly improves survival, making it the preferred approach, the authors state.

The customary treatment for AML involves an initial "induction" phase that uses a combination of chemotherapy agents to put the disease into a first remission. The second stage of treatment, called "consolidation," is undertaken with the goal to cure the disease.

Consolidation options include additional rounds of chemotherapy; autologous transplantation (which uses a patient's own blood stem cells); or allogeneic SCT (in which compatible donor cells are transplanted).

Traditionally, the treatment offered to patients has largely been based on a chromosome analysis of their AML cells. For AML with "good-risk" chromosome changes, additional chemotherapy or an autologous transplant is usually recommended. For AML with "poor-risk" changes, allogeneic SCT is usually recommended. For AML with "intermediate-risk" changes (the largest group), there has been no consensus on the best treatment.

In the new study, researchers confirmed that, consistent with current practice, patients with poor-risk AML benefited significantly from an allogeneic transplant performed in first remission, while those with good-risk disease did not benefit from the procedure. For patients with intermediate-risk disease, who account for nearly half of all adult AML patients, allogeneic transplant in first remission proved to be the most effective strategy, the investigators found.

"Allogeneic transplants have been shown to be very effective for many AML patients with aggressive disease, but such transplants are often associated with serious side effects and complications. It has never been comprehensively shown which patients stand to benefit significantly from the procedure," says the study's lead author, John Koreth, MBBS, DPhil, of Dana-Farber.

"For patients with poor- and good-risk AML, our study provides reassurance that the current treatment recommendations are correct. Our finding that people with intermediate-risk AML benefit significantly from allogeneic transplant in first remission should establish it as the preferred treatment for this group."

In the study, Koreth and his colleagues analyzed the results of 24 clinical trials involving more than 6,000 AML patients from age 18 to 60. They found that over the long term, patients with poor- and intermediate-risk AML who received allogeneic stem cell transplants in first clinical remission were more likely to be alive than those who received alternative therapies, and were less likely to suffer disease relapse.

While the findings support the use of chromosome analysis — the classification of AML cases as either poor-, intermediate-, or good-risk — for guiding treatment, "There remains a need to further individualize the allogeneic SCT decision, based on factors like patient age, overall health, and other considerations, including newer molecular tests," Koreth says.

The study's senior author is Corey Cutler, MD, MPH, of Dana-Farber.

The study's co-authors include Martha Wadleigh, MD, Daniel DeAngelo, MD, PhD, Richard Stone, MD, Joseph Antin, MD, and Robert Soiffer, MD, Dana-Farber; Richard Schlenk, MD, and Hartmut Dohner, MD, University Hospital of Ulm, Germany; Kenneth Kopecky, PhD, and Frederick Appelbaum, MD, Fred Hutchinson Cancer Research Center; Sumihisa Honda, PhD, Nagasaki University, Japan; Jorge Sierra, MD, PhD, of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Benjamin Djulbegovic, MD, PhD, University of South Florida; and Hisashi Sakamaki, MD, PhD, of Tokyo Metropolitan Komagome Hospital, Japan.

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