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Studies Assess Role of Genetics, Modified Treatment Strategies to Improve Outcomes and Reduce Toxicity for Patients with Blood Cancers

PR Newswire



ATLANTA, Dec. 8, 2012 /PRNewswire-USNewswire/ -- Research identifying genetic factors that affect survival of patients with blood cancers and evaluating the effectiveness of modified treatment strategies to improve outcomes while reducing toxicity will be presented today at the 54th Annual Meeting of the American Society of Hematology (ASH).

While the cancer research community has seen many significant therapeutic advances over the last decade, only recently have investigators identified how patients' individual genetic makeup influences their short- and long-term response to therapy, demonstrating that while the disease may respond positively to therapy, the patient may not. Current studies take these insights a step further, examining specific patient subpopulations to determine their risk for negative outcomes and whether early preventive interventions or treatment adjustments may help avoid treatment-related toxicity.

"Data presented today offer important insights into how and why patients respond to blood cancer treatment," said William G. Woods, MD, moderator of the press conference, Pediatric Hematology/Oncology Director, and the Daniel P. Amos Children's Chair of the Aflac Cancer Center and Blood Disorders Service at Children's Healthcare of Atlanta. "Findings from these studies help further support the notion of one day personalizing cancer treatment to the individual, rather than to the disease, to improve survival and reduce toxicity."

This press conference will take place on Saturday, December 8, 2012, at 10:00 a.m. EST.

WT1 SNP rs16754 Genotype Predicts Treatment Related Mortality (TRM) in African-American and Asian Pediatric AML Patients: A Report From the Children's Oncology Group [Abstract 1385]

New research suggests that the presence of a specific genetic marker, known as WT1 SNP rs16754, may be associated with reduced toxicity from chemotherapy in African-American and Asian children with acute myeloid leukemia (AML).

AML, the second most common form of leukemia in children, is a blood cancer in which the bone marrow makes a large number of abnormal white blood cells that crowd out other healthy blood cells over time, leading to infection, anemia, or excessive bleeding. Although 60 to 70 percent of children with AML achieve long-term remission after treatment with multi-agent chemotherapy, the treatment-related mortality (TRM) associated with this intensive treatment regimen remains a major concern for this patient population. Recently, researchers have developed models that use sophisticated genome sequencing techniques to better understand how patients' genetic makeup may influence their risk of TRM.

The WT1 gene, a tumor suppressor that regulates cell growth, can be subject to "loss-of-function" mutations that lead to the development of AML. Unlike genetic mutations, single-nucleotide polymorphisms (SNPs, naturally occurring variations in the DNA that determine an individual's unique genetic makeup) are not typically thought to play a role in leukemia development or treatment response. However, researchers recently discovered that the presence of SNP rs16754 in the WT1 gene is correlated with improved outcomes in pediatric patients with AML. Based on the fact that the frequency of SNP rs16754 varies by race, researchers assessed the effect of this SNP on outcomes in specific ethnic patient groups.

To determine if the presence of SNP rs16754 affected survival, remission, relapse risk, and TRM in pediatric AML patients of different ethnicities, a team of investigators analyzed the DNA of 492 children with AML enrolled in the CCG-2961 protocol, a Phase III Children's Cancer Group trial. The intensive treatment regimen delivered to patients during CCG-2961 allowed researchers to study the effects of ethnicity on patient outcome, while minimizing non-biological influences such as access to care or oral medication compliance. Of the 492 patients, 138 (28%) had the SNP rs16754 (SNP+). After stratifying the patients by ethnicity, the investigators found that the presence of SNP rs16754 varied by race, with 53 percent of Asians, 34 percent of Hispanics, 25 percent of Caucasians, and 21 percent of African Americans carrying the genetic variation. The SNP+ patients had higher five-year overall survival rates than those without the variation (SNP-) (61% vs. 44%). Within each racial subgroup, the five-year overall survival rate was higher in the SNP+ patients.

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