ASH: Leukemia Mutations Predict Response to Stem Cell Grafts

December 13, 2006

ORLANDO -- For some patients with acute myeloid leukemia, an unfavorable prognostic marker could mean a better response to allogeneic stem cell transplantation, a German-Austrian research team reported here.

ORLANDO, Dec. 13 -- For some patients with acute myeloid leukemia, an unfavorable prognostic marker could mean a better response to allogeneic stem cell transplantation, a German-Austrian research team said here.

In a study of 872 patients with AML with the normal karyotype, those who had a specific combination of two common genetic mutations were more likely to achieve complete remission after chemotherapy, reported Richard Schlenk, M.D., of the University of Ulm in Germany.

On the other hand, those with presumably unfavorable complications were more likely to benefit from stem cell transplantation after the first complete remission, Dr. Schlenk said at the American Society of Hematology meeting, speaking on behalf of colleagues in the German-Austrian Study Group.

"In our study, specific genotypes emerged as important predictors of response to therapy and survival in AML patients," Dr. Schlenk said. "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."

Dr. Schlenk and colleagues looked at mutations in the leukemic cells of 872 patients enrolled in four clinical trials. They focused on common mutations that have been identified as molecular markers for AML in patients with a normal karyotype.

"Most recent studies focused on the prognostic value of single markers, not taking into account their potential interactions," Dr. Schlenk said. "In addition, little is known about the predictive value of these markers on post-remission therapy."

They looked at the prognostic effect of the mutations on responses to induction therapy, and to relapse-free and overall survival. They also examined the predictive value of the mutations on survival following different post-remission therapies.

They patients ranged in age from 16 to 60 years, and all patients with an HLA-matched family donor were assigned to allogeneic stem cell transplantation while in first complete remission.

The authors found that the most common mutation was NPM1, occurring in 53% of samples, followed by FLT3-ITD, in 31%, FLT3-TKD in 11%, CEBPA in 14%, MLL-PTD in 8%, and NRAS in 13%.

The complete remission rate was 76%. In logistic regression analysis, combination of the NPM1+ and FLT3-ITD- genotype was associated with successful induction (P