Back to Oncology Articles
Monday 29th November, 2004
The results suggest that those receiving more intense therapies are
associated with a longer disease free survival than those receiving lower-dose
COLUMBUS, Ohio ? New research is helping select which therapies
improve the chances of remission in the largest category of people
affected by acute myeloid leukemia (AML) ? those whose cancer cells have
The findings suggest that people receiving more intense therapies are
more likely to enter remission and to remain there longer than those
receiving lower-dose therapies.
The study was published online Nov. 8 by the Journal of Clinical
The Cancer and Leukemia Group B (CALGB) study was initiated by
researchers at the Ohio State University Comprehensive Cancer Center ?
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
(OSU CCC-James). It is part of a larger CALGB cytogenetic trial chaired
by Clara D. Bloomfield, professor of internal medicine and the William
G. Pace III Professor in Cancer Research, OSU Cancer Scholar and senior
adviser to the OSU cancer program.
Unexpectedly, the current study also found that patients who had an
enlarged spleen at the time of their initial treatment were less likely
to enter remission. AML patients are in remission when leukemic cells
are not microscopically detectable among their bone-marrow cells.
?These preliminary findings raise the question of whether additional
treatment directed specifically to the spleen might improve remission
rates,? says first author Sherif S. Farag, assistant professor of
internal medicine and a medical oncologist with the OSU CCC-James. ?At
this point, this is just a hypothesis that needs to be tested, but it
may be that the spleen is a sanctuary site for leukemic cells and needs
?This study is important because it is
the first large study to examine different types of therapy that is
restricted to patients with normal chromosomes. Yet, they make up
the largest single group of people with AML.?
A diagnosis of AML routinely includes studying patients? leukemic
cells for chromosome damage, a process known as cytogenetic analysis.
The information helps determine the best therapy and a patient?s chance
of remission and cure. But 40 percent of AML patients have leukemic
cells with normal-looking chromosomes. Without chromosomal abnormalities
to guide treatment, several therapies are usually used.
?This study is important because it is the first large study to
examine different types of therapy that is restricted to patients with
normal chromosomes,? says Krzysztof Mr?ek, an internationally
recognized cytogeneticist, research scientist in internal medicine and
one of the paper?s coauthors. ?Yet, they make up the largest single
group of people with AML.?
The multi-institutional study analyzed data from 490 patients treated
for AML through five clinical trials conducted over nearly 20 years.
Only adult patients under 60 years of age were included.
Overall, three quarters of the patients achieved complete remission.
The average overall survival for the patients was 1.9 years, with 35
percent of patients still alive and disease-free after five years (these
patients were considered cured).
Are you a doctor or a nurse?
Do you want to join the Doctors Lounge online medical community?
Participate in editorial activities (publish, peer review, edit) and
give a helping hand to the largest online community of patients.
Click on the link below to see the requirements:
Doctors Lounge Membership
The researchers first compared the outcomes of patients receiving one of
two drug regimens given to bring the disease into remission. The study
compared 350 patients receiving the drugs cytarabine plus daunorubicin
to 140 patients receiving cytarabine plus increasing doses of both
daunorubicin and etoposide.
They found that both treatments induced remission about equally well.
But to their surprise, they also found that patients with a normal
spleen were four times more likely to enter remission than patients with
an enlarged spleen, regardless of therapy.
The researchers then looked at the second phase of treatment, known
as intensification therapy, which is intended to keep patients in
remission and to enhance the rate of cure.
The study compared four intensification therapies. Of these, the two
more-intense therapies each produced longer remission periods and a
better chance of cure than did the two less-intense therapies. That is,
four cycles of high-dose cytarabine or one cycle of high-dose cytarabine
and etoposide followed by stem-cell transplant were more effective than
was one cycle of high-dose cytarabine alone.
?There are many different approaches to post-remission therapy, and
they include using fewer cycles of high-dose cytarabine or reducing the
dose of the drug, but our study suggests these treatments are inferior,?
At the same time, the study suggested that using very high doses of
cytarabine may also be unnecessary. Using an intermediate dose seems
equally effective but has fewer side effects, which can include toxicity
to the kidneys and brain.
?This has been suspected, but it hasn?t been carefully studied,?
Farag says. ?Again, we need a larger randomized study in the future to
verify this, but our data show that we don?t need to push the dose to
the maximum to have equal anti-leukemic effect.?
The study also suggested, however, that while two of the four
therapies might produce longer remission periods?also known as periods
of disease-free survival?no one treatment improved overall survival. The
study followed patients for an average 7.4 years. ?More research and
some different strategies are still needed to give higher cure rates in
these AML patients,? Farag says.
Funding from the National Cancer Institute (NCI) supported this
study. The CALGB is a multicenter NCI clinical trials group.
Sherif S. Farag, Amy S. Ruppert, Krzysztof Mr?ek, Robert J. Mayer,
Richard M. Stone, Andrew J. Carroll, Bayard L. Powell, Joseph O. Moore,
Mark J. Pettenati, Prasad R.K. Koduru, Judith Stamberg, Maria R. Baer,
AnneMarie W. Block, James W. Vardiman, Jonathan E. Kolitz, Charles A.
Schiffer, Richard A. Larson, and Clara D. Bloomfield (tentatively
scheduled for the 1/20/2005 print issue). Outcome of Induction and
Postremission Therapy in Younger Adults With Acute Myeloid Leukemia With
Normal Karyotype: A Cancer and Leukemia Group B Study. JCO published
November 8, 2004, 10.1200/JCO.2005.06.090