Acute myeloid leukemia ( AML ) can be cured, but only in about 20-30 percent of patients, depending on a number of prognostic factors. A team of German researchers has explored how treatment responses could vary based on the genetic makeup of leukemia cells.

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 patients with acute myeloid leukaemia.” said Richard Schlenk, 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.”

Source: American Society of Hematology ( ASH ) – Meeting, 2006


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