Blood cancers

New model of risk stratification for ALL in kids

The presence or absence of two microdeletions combined with minimal residual disease (MRD) and National Cancer Institute (NCI) risk can improve early stratification of children with acute lymphoblastic leukaemia (ALL).

The Australian-led research involving 475 children with non-high risk precursor B-cell ALL enrolled in the ANZCHOG study ALL8 found IKZF1 and P2RY8-CRLF2 deletions were predictive of relapses.

Each deletion had a significant effect on relapse free survival, event free survival and overall survival. Combined, the two deletions were more effective at discriminating relapse than MRD (>5×10-5 at day 33) and NCI high risk.

A risk stratification score (RS0, RS1 or RS2+) using the presence of one or two deletions, MRD and NCI was then developed and used to identify a sub-group of patients previously classified as medium risk who were likely to relapse.

The risk score was also validated in an independent cohort of medium risk B-cell precursor ALL patients from The Netherlands.

Co-author Dr Toby Trahair, a paediatric haematologist and oncologist at the Children’s Cancer Institute and Kids Cancer Centre, told the limbic the improved stratification meant some children would now receive more intensive treatment earlier.

“It’s much better to prevent relapse by treatment rather than have to treat somebody at relapse.  So in the next generation of clinical trials and treatment for children with leukaemia, we are going to build in strategies to try and identify these higher risk patients at early time points.”

He said the largest number of relapses come not from the high risk patients but from those determined to be medium risk using clinical features (NCI) and the leukaemia’s response to treatment (MRD).

He said the bonus was the new risk model relied on laboratory techniques that were easy to use and would be easy to implement.

“The technology used to identify small deletions is increasingly available and this paper is important because it shows we need to be looking for these microdeletions in ALL. Much more accurate risk prediction will ensure the best therapy and the lowest chance of relapse.”

“It’s an exciting new area in that we do know that some patients with microdeletions have genetic changes that are targetable.  And so a whole sub- group of leukaemia we are now starting to call Philadelphia like leukaemia, often have targetable genetic changes, some of which do respond to targeted treatments.”

He said ANZCHOG study ALL10 would be further exploring the risk model and a combination of a targeted therapy such as imatinib and conventional chemotherapy.

“If we find a targeted agent works well with acceptable toxicity and improved cure rates, we will continue to use it.”

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