I am sorry to hear the teenager has had a difficult clinical course. As you know, in the current EsPhALL/Children’s Oncology Group study for Ph+ ALL, MRD assessment is done using IgH/TCR PCR and BCR-ABL1 PCR is not used for clinical decision making. Having that practice, I would send the patient to BMT now. You said donor options are not good. If he was here with us, we would take him to BMT with haploidentical donor (likely a parent). Is it an option at your center? If this is CML blast crisis, not Ph+ ALL, my approach would be the same. Although children with CML in advanced stages seem to do better (Eur J Cancer. 2019 Jul;115:17-23), BMT would give him the best chance. Switching to ponatinib was appropriate. Serious cardiovascular events that are seen in adults have not been reported in children so far (Br J Haematol. 2020 Apr;189(2):363-368) but Phase 1 studies are ongoing. If he needs to continue TKI and is truly resistant to ponatinib, empirical switch to other TKI like nilotinib or bosutinib may be an option, but I am not sure about it. Again, I think BMT now with negative IgH/TCR PCR would be the best option.