Gene Mutations Predict Treatment Outcomes In Patients With Leukemia

Curing acute myeloid leukemia
(AML), a rapidly progressing bone-marrow cancer, is possible, but only in
about 20-30 percent of patients, depending on a number of prognostic
factors. A team of German researchers who explored how treatment responses
could vary based on the genetic makeup of leukemia cells are sharing their
findings today during the 48th Annual Meeting of the American Society of
Hematology (ASH(TM)).



"The treatment of leukemia has advanced remarkably over the last 20
years," said ASH President Kanti R. Rai, MD, of Long Island Jewish Medical
Center and the Albert Einstein College of Medicine. "This study shows the
possibility of refining therapy even further, so it's no longer a 'let's
try this and see if it works' approach; instead, it offers the possibility
to use molecular genetics approaches to improve treatment outcomes."



The researchers evaluated the leukemia cells of 872 AML patients ages
16- 60 with a normal genetic makeup, which occurs in about half of those
with the disease. The most common genetic abnormalities found in the cancer
cells were NPM1 mutations (in 53 percent of the samples), FLT3 mutations
(in 31 percent), and CEBPA mutations (in 14 percent).



More than three-quarters of the patients experienced a complete
remission after chemotherapy, and the NPM1 and CEBPA genes were most
associated with success. Age (less than 48 years), the availability of a
family member donor match for stem cell transplant, and the presence of the
NPM1 and CEBPA mutations were predictors for both relapse-free survival and
overall survival. Also of significance were internal tandem duplications on
the FLT3 gene, known as FLT3-ITD. When paired with the NPM1 mutation, the
FLT3-ITD mutation canceled the favorable impact of NPM1.



While in remission, 143 of the 171 patients who had a matched family
donor underwent stem cell transplantation, a therapy strategy that offers
one of the best chances of a cure, but also carries some of the greatest
risks. Of those with the combination NPM1 positive and FLT3-ITD negative
genotype, about 60 percent remained relapse-free after four years, whether
or not they had a stem cell donor. Of those with other combinations of NPM1
and FLT3 mutations, the relapse-free rates dropped to 47 percent for those
with a donor, and further still for those without a donor to 23 percent.



"In our study, specific genotypes emerged as important predictors of
response to therapy and survival in AML patients," said Richard Schlenk,
MD, head of the Clinical Trials Office of the German-Austrian AML Study
Group (AMLSG) at the University of Ulm and lead study author. "The results
may help doctors choose the best option from among the existing treatments
for their patients and pave the way for new treatments aimed at unfavorable
mutations."



The American Society of Hematology (hematology/) is the
world's largest professional society concerned with the causes and
treatment of blood disorders. Its mission is to further the understanding,
diagnosis, treatment, and prevention of disorders affecting blood, bone
marrow, and the immunologic, hemostatic, and vascular systems, by promoting
research, clinical care, education, training, and advocacy in hematology.


American Society of Hematology

hematology/

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