EBMT 2023 | Improving risk stratification in ALL with risk scores & genomic studies to personalize therapy

We’re starting to become a little more sophisticated in our risk stratification. A lot of this we have known that MRD is a very important factor, but also, we have various cytogenetic abnormalities, particularly MLL rearrangement, complex cytogenetics and low hyperdiploidy, less than 40 chromosomes. We know those still remain important prognostic factors that determine our treatment and probably also the diagnostic white cell count. A very high diagnostic white cell count again, means a less good biology of the of the disease. But the thing we’re doing that’s different, and this work has been pioneered by Anthony Moorman of our UK group, is to do a mathematical formula assigning different weights to these various adverse prognostic factors and this comes up with an overall risk score and that can be helpful in deciding whether to continue with chemotherapy or move towards transplant. So that’s published in children and validated, there’s a discovery set and then there’s a confirmation set, the next trial that we perform in the UK will use a sort of adult version of that risk score to help us make transplant decisions

Whilst we have a risk score, we still need to validate it. This is a more sophisticated way of looking at risk in patients with ALL. Clearly, we need to look a bit deeper and lots of groups, the pediatricians are perhaps slightly ahead of us as usual, but other groups like Anthony Moorman and Adele Fielding and of course other people in the United States, what they’re looking at are genomics. We hope with those genomic studies that we will find certain patterns, certain patterns of abnormal genomics that enable us to pull out the patients who don’t have the conventional risk factors but do have adverse genetics and give them different treatment. These are people who should have an allograft in first remission or possibly CAR T-cells. We have a lot more work to do there. But you know, for instance, in the ALLTogether study, the massive, pan-Europe pediatric ALL study, there’s built in genomics and we’re going to learn a lot about how to individualize patient treatment.