Pediatric ALL with chromosome 21 abnormality needs more aggressive treatment

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Children whose leukemia cells have amplification of a portion of chromosome 21 may require more aggressive treatment for acute lymphoblastic leukemia (ALL) than children without this gene amplification, according to a recent study by the Children's Oncology Group.

“This helps identify patients who need more therapy than they may otherwise get,” said Stephen Hunger, MD, an investigator at the University of Colorado Cancer Center and pediatrics professor at the University of Colorado School of Medicine.

Hunger notes that this genetic abnormality, first described in 2003, has been found in about 2% of patients with pediatric ALL. Initial reports described poor outcomes for small groups of children with this abnormality, but the current study is by far the largest and shows the importance of this genetic abnormality even with modern treatments. The study, which was published in the Journal of Clinical Oncology (2013; doi:10.1200/JCO.2013.49.1308), documents the treatments and outcomes of more than 8,000 cases of pediatric ALL.

“What we found is that when this genetic abnormality is present in children with good risk features who get a standard level of treatment, there is more treatment failure than with similar low-risk kids who do not have this genetic marker. But with kids whose risk features already dictate more aggressive treatment, this genetic abnormality does not seem to be associated with a worse outcome, because kids are already getting the appropriate treatment. Recognizing this abnormality could help us treat even otherwise low-risk kids more aggressively up-front, leading to improved cure rates,” Hunger said.

Specifically, the genetic abnormality is defined as four or more copies of the gene RUNX1, located on an abnormal chromosome 21. This amplification is already detected as a byproduct of another genetic test standard in pediatric ALL, namely a test for fusion of this RUNX1 gene with the gene ETV6.

“In a sense, the testing comes for free with other testing you're already doing,” Hunger said.

A study published by the same group in 2012 showed that pediatric ALL cure rates are at or above 90.4%.

“In early 1960s this disease was incurable,” Hunger said. “Then in the late 1960s, the cure rate was 10%. Now 90% of children and adolescents diagnosed with ALL will be cured. Still, a 90% survival rate is little consolation to the 10% of families whose child does not survive. There's still more work to be done.”
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