gene mutations predict treatment outcomes in...

[Lani]

leukemia Hopefully coming soon for breast cancer as well to avoid "one size fits all" method of treatment:

Gene Mutations Predict Treatment Outcomes in Leukemia

Allison Gandey
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January 11, 2007 (Orlando) –- Researchers from an acute myeloid leukemia study group have shown that treatment responses vary depending on the genetic makeup of leukemia cells, and they recommend screening as part of the initial workup in younger adults with normal karyotype acute myeloid leukemia. Presenting at the recent American Society of Hematology (ASH) 48th Annual Meeting and Exposition, the group demonstrated that mutations in NPM1, FLT3, and CEBPA can affect response to therapy and can serve as important predictive markers.
"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 to improve treatment outcomes," the society's president, Kanti Rai, MD, from the Long Island Jewish Medical Center, in New Hyde Park, New York, and the Albert Einstein College of Medicine, in the Bronx, New York, told reporters.

The researchers looked at 872 patients with acute myeloid leukemia and a normal karyotype — a genetic makeup that typically occurs in about half of those with the disease. The most common genetic abnormalities observed in the cancer cells were NPM1 mutations, seen in 53% of the samples; FLT3 mutations, found in 31%; and CEBPA, in 14%.

Using Molecular Genetics to Tailor Therapy

In a news briefing about the plenary session study, lead author Richard Schlenk, MD, head of the clinical trials office of the German-Austrian Acute Myeloid Leukemia Study Group at the University of Ulm, reported that more than three quarters of the patients had complete remission after chemotherapy. 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.

Internal tandem duplications of the FLT3 gene, known as FLT3-ITD, also had an important effect on outcome. When paired with the NPM1 mutation, the FLT3-ITD canceled the favorable impact of NPM1.

Of the 666 patients achieving a complete remission after induction therapy, 171 had a matched family donor, and 143 of these received an allogeneic stem-cell transplant. In survival analyses, the researchers included the variable availability of a matched family donor on a strict intent-to-treat basis.

Of those with the combination NPM1 and FLT3-ITD-negative genotype, 61% remained relapse-free after 4 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% for those with a donor and further still for those without a donor, to 23%.

"For patients with an unfavorable outcome, we should think to include allogeneic transplantation with unmatched unrelated donors after first complete remission," Dr. Schlenk told Medscape during an interview. "And for the favorable-outcome group, we need to explore other treatment strategies." He noted that while critics might argue that these findings are from a nonrandomized trial, his group used genetic randomization. "Nearly 25% of our cohort had a family donor, and 85% had an allogeneic transplant at first complete remission."

ASH 48th Annual Meeting: Abstract 4. Presented December 10, 2006.