Now we know about this all the clonality, we really have to take that into account by having different techniques to look at MRD because as I mentioned, we looked at the leukemia-associated immunophenotypes at diagnosis and then we followed only that phenotype during therapy in MRD. And then of course we can miss the upcoming clones that may be caused by clonal evolution. The nice thing about this method is that you can clearly follow the dominant clone at diagnosis and see if it’s effectively treated by the new treatment...
Now we know about this all the clonality, we really have to take that into account by having different techniques to look at MRD because as I mentioned, we looked at the leukemia-associated immunophenotypes at diagnosis and then we followed only that phenotype during therapy in MRD. And then of course we can miss the upcoming clones that may be caused by clonal evolution. The nice thing about this method is that you can clearly follow the dominant clone at diagnosis and see if it’s effectively treated by the new treatment. So that’s actually an advantage. But the disadvantage is that you need the diagnostic sample and that you maybe miss the clones that are upcoming. So other groups use the more different-from-normal approach and that’s when they just look at any changes in the flow patterns that are not there in normal bone marrow and then they call any MRD, MRD. But the disadvantage of that is that you need a lot of experience on how these flow patterns look like in order to use them. But what we are doing now is we are combining both techniques. So we call it a LAIP-based different-from-normal technique and then we can not only follow the LAIP at diagnosis but also see any emerging clones and especially in trials that you cannot acquire a lot of diagnostic samples so you don’t have any LAIP at diagnosis, this is also giving the opportunity to have more MRD results. So that is actually in the next HOVON trial. We are going to analyze all this data that we have gathered about the LAIP and the different-from-normal and see if it really improves the MRD by flow cytometry.