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Rosemary Sutton, PhD
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Children’s Cancer Institute

Researchers say they have developed a more accurate risk scoring system for children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) who are typically thought to have standard- or medium-risk disease.

The scoring system includes 3 factors associated with higher-risk BCP-ALL—the presence of high-risk ALL gene microdeletions, having minimal residual disease (MRD) greater than 5 x 10-5 at day 33, and being high-risk according to National Cancer Institute (NCI) classification.

The researchers found that children with 2 or more of these characteristics were most likely to relapse or die within 7 years of treatment initiation.

On the other hand, children without any of the 3 characteristics had high rates of relapse-free survival (RFS) and overall survival (OS).

Rosemary Sutton, PhD, of Children’s Cancer Institute in Sydney, New South Wales, Australia, and her colleagues devised this risk scoring system and described it in the British Journal of Haematology.

The researchers created their system with the help of data from 475 patients (ages 1 to 18) who had BCP-ALL and were considered non-high-risk. The patients were enrolled on the ANZCHOG ALL8 trial.

Dr Sutton and her colleagues noted that children with standard- or medium-risk BCP-ALL typically receive less intensive treatment than children with high-risk BCP-ALL. However, some of the standard- and medium-risk patients do relapse.

“For the standard- to medium-risk group, we needed more information to get a better handle on the biology of the child’s cancer to better determine their risk,” Dr Sutton said. “So we supplemented MRD results with 2 other pieces of patient information—the presence or absence of specific gene microdeletions and a score called the NCI risk, based on age and white blood cell count.”

“We tested for microdeletions in 9 genes involved in leukemia and found that 2 of the genes—IKZF1 and P2RY8-CRLF2—were important predictors of relapse.”

The researchers combined patients with IKZF1 intragenic deletions, P2RY8-CRLF2 gene fusion, or both into a “high-risk deletion group.”

And the team based the scoring system on 3 factors—the high-risk deletion group, MRD >5 x 10-5 at day 33, and high risk according to NCI risk classification. Patients received 1 point for each of these factors.

The RFS rate was 93% for patients with a score of 0, 78% for those with a score of 1, and 49% for patients with a score of 2 or 3. The OS rate was 99%, 91%, and 71%, respectively.

The researchers said their scoring system provided greater discrimination than MRD-based risk stratification into a standard-risk group—which had an RFS of 89% and an OS of 96%—and a medium-risk group—which had an RFS of 79% and an OS of 91%.

Study author Toby Trahair, MBBS, PhD, of Sydney Children’s Hospital in Randwick, New South Wales, said this scoring system could make a big difference to the success of BCP-ALL treatment.

“We are always trying to improve how we diagnose and treat children with this most common childhood cancer,” Dr Trahair said. “This risk score will mean doctors can fine tune a child’s risk category and so fine tune their treatment. It will mean more kids can conquer this horrible disease, which, only 50 years ago, had survival rates of close to 0.”

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