Thank you for this interesting case. To summarize, this is CP CML transplanted after imatinib resistance and salvage with dasatinib. Post transplant there was very low MRD treated with dasatinib once again at what sounds like standard doses (BSA dosing) but 18mo hence there is molecular persistence/increase to a level approaching loss of MMR on the IS.
My reaction:
1/ I might try to work with TKIs a bit more- is there room for dose escalation of dasatinib? His MRD has been well controlled from either a partial GVL effect or a TKI effect or both. I am impressed by the very low level of MRD and might wonder if slightly more TKI effect might bring deeper MR in the presence of any residual GVL.
2/ Mutation testing may be of benefit. Given IM resistance and somewhat longer dasatinib exposure this may help in the decision to use more dasatinib, consider switching to nilotinib if a select mutation (DAS resistant/NIL sensitive) or another choice, etc. (see #3)
3/ Ponatinib is an option; one may be concerned about AEs and there is only persistent MRD; I would consider ponatinib if the disease were to continue to proliferate or a t315i mutation was noted.
4/Overall it is the case that GVL has not carried the day for this case; of course DLI if available may benefit in this MRD setting although the timing is late and full chimerism and full immune reconstitution of donor hematopoiesis is likely in place. Hence consideration of a second transplant, if feasible, could be weighed against the option of stable MRD on a TKI if manipulation works (dose increase, switch, etc). If the disease is proliferating, there is a t315i mutation, or for patient choice there is a reasonable case to consider re-transplant.
I will open the floor up for comments on the conditioning regimen while I poll some colleagues; I would not be the right person to help choose that….
Comments? Suggestions? Agreement? Disagreement?