Australasian Science: Australia's authority on science since 1938

Missing DNA Fragments Point to Child Leukaemia Relapse

Australian researchers have developed a new risk-scoring system for children with leukaemia that will allow doctors to predict the chance of relapse of a subgroup of children currently hidden in a lower risk group.

The researchers discovered that the presence of specific gene microdeletions found only in leukaemia, when combined with two other tests, provided a more accurate way to categorise patient risk.

The study, published in the British Journal of Haematology, tested 475 children with non-high-risk B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), a subtype of acute lymphoblastic leukaemia (ALL), the most common childhood cancer with survival rates typically near 90%.

“Children in the standard and medium-risk category in the study were given less intensive treatment than high-risk patients, but about one in six of them relapsed,” said study leader A/Prof Rosemary Sutton of the Children’s Cancer Institute. “Obviously, some children needed more intensive treatment than previously thought, but which ones?”

The researchers developed a new risk score that builds on the minimal residual disease (MRD) test, which can detect just one cancer cell in a million bone marrow cells surviving cancer treatment. MRD alerted doctors that some children with leukaemia on the trial had a very high risk of relapsing. Consequently they were treated very intensively with chemotherapy and bone marrow transplants, and the survival rate of this subgroup doubled.

But MRD alone is not enough. “So we supplemented MRD results with two other pieces of patient information, the presence or absence of specific gene microdeletions and a score called the NCI (National Cancer Institute) risk, based on age and white blood cell count,” Sutton said. “We tested for microdeletions in nine genes involved in leukaemia and found that two of the genes, IKZF1 and P2RY8-CRLF2, were important predictors of relapse.”

These measures were combined to calculate a risk score for each patient of 0 (no risk factors) to 2+ (several). The study found that children with a 2+ score were most likely to relapse or die within 7 years.

The same microdeletions were important for predicting relapse in a cohort of Dutch children with leukaemia, and the new scoring system was validated by researchers in The Netherlands.

The researchers say that if the new risk score system is adopted in future, doctors could give children with a 2+ risk more intensive treatment to improve their survival chances.