How would you treat a pediatric or AYA patient with Ph-like ALL with induction failure?

This is a bit of a complicated discussion. There are 2 major subtypes of Ph-like ALL, 1) CRLF2-rearranged B-ALL; 2) non-CRFL2 B-ALL which is characterized by fusions in a variety of genes including ABL1, ABL2, JAK2, etc.

If you have a patient with a documented fusion in ABL1, ABL2, and others which are known to provide sensitivity to ABL1 TKIs (such as dasatinib, ponatinib), my approach for induction failure will be to add the TKI to the salvage regimen (such as blinatumomab + TKI, or chemo + TKI).

If you have a patient with a documented fusion in JAK2, EPOR, etc. which are known to provide sensitivity to JAK inhibition such as with ruxolitinib, one could consider adding ruxolitinib; however, very limited clinical data is available in this...