Genetic profile IDs leukemia patients for high-dose chemotherapy

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Persons with acute myeloid leukemia (AML) who harbor specific gene mutations may have improved overall survival with higher doses of chemotherapy, researchers have found.

Hillard M. Lazarus, MD, of the Seidman Cancer Center at University Hospitals Case Medical Center in Cleveland, Ohio, and colleagues performed a mutational analysis of 18 genes in 398 patients younger than age 60 years who had AML and who were randomly assigned to receive induction therapy with high-dose or standard-dose daunorubicin. They validated their prognostic findings in an independent set of 104 patients.

As the investigators reported in The New England Journal of Medicine (2012;366:1079-1089), mutations in two genes (DNMT3A and NPM1) and translocations to the MLL gene (movement of part of one gene to another gene) predicted an improved outcome with the high-dose daunorubicin induction chemotherapy.

In 2009, Lazarus and colleagues found that compared with the standard dose of daunorubicin (45 mg per square meter of body-surface area), a high dose (90 mg per square meter) resulted in a higher rate of complete remission (70.6% vs 57.3%) and improved overall survival (median 23.7 months vs 15.7 months) in previously untreated AML patients between the ages of 17 and 60 years (N Engl J Med. 2009;361:1249-1259).

Regarding the latest results, “These significant findings will provide an important new tool to predict patients' response to cancer-fighting therapies and will help physicians avoid overtreating some patients and undertreating others,” explained Lazarus in a statement.

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