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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
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
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
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,"
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.