Mild reticulin fibrosis (MF-1) without collagen fibrosis in both his diagnostic marrow and his most recent marrow. I have not been comfortable restarting any TKI at this point because of his persistent profound cytopenias (Plt <10, ANC <100 for 10+ weeks).

Hi there, I opted to start with dasatinib as first line TKI for this patient as he was an older teenager. Since dasatinib may be associated with faster and deeper molecular response than imatinib, I figured it may have a better chance at TFR later down the line. And dasatinib 100mg is standard FDA approved dosing (BSA 1.8)

Thank you so much for your thoughts and recommendations.

We are moving forward with allo HCT as soon as possible. Trialed GCSF for 14 days with no response. Marrow still <10% cellularity, predominantly erythroid precursors. BCR ABL PCR down to 5% without any other intervention since last marrow 1 month prior (off TKI >2 months now).

Any thoughts on utility of starting asciminib to try to get as much disease control as possible prior to transplant? I see both pros and cons.

Thank you for your response.

Patient fortunately has good donor options and is a good candidate for transplant, so we are moving forward with allo BMT.

We trialed GCSF 5 mcg/kg for 2 weeks with no response (ANC remained 40-60 throughout this time) so have now stopped it.

I repeated a bone marrow 2 weeks ago which showed cellularity <10%. His BCR ABL PCR is interestingly down quite a bit- only 5.474% (major breakpoint e13a2, with 0.011% minor breakpoint e1a2) compared to 24% (0.020% minor breakpoint) in his marrow back in May. Dasatinib has been on hold since early April.

Myeloid NGS panel and BCR ABL mutation analysis were sent from most recent marrow, and are still pending.

My one question at this time is whether to start asciminib to try to get any more disease control prior to BMT, or to keep him off TKI so as to not further suppress any chance of possible delayed spontaneous recovery.

Thank you!

Hi, i agree with others that this is an ominous combination of severe myelosuppression coupled with response albeit limited. I do not see ABL mutation testing, this may be informative for any therapy in the short or long term; it is intriguing there was stability followed by severe cytopenias, suggesting expansion of different clones. Historically transformation risk is high in these cases of severe myelosuppression and limited response, especially as therapy is difficult if at all and dose intensity drops. Growth factors may be tried to stabilize/bridge. Allografting seems the right path especially as disease burden is rising.

Marrow is empty and biopsy has been done. Although CML seems to have responded to DAS, normal hemopoiesis has not recovered.

This child is pancytopenic and at risk. G-CSF could be tried for a week or so to see if there is any response and this will give you an idea if there is any functioning reserve. I would not wait 3 months to see if platelets respond to eltrombopeg.

If no response to the G-CSF, I would not wait around for a problem. A lower dose of DAS or a drug switch will not allow recovery of what is not there. Proceed with an allograft. Waiting just increases the risk of infection, bleeding and/or platelet refractoriness developing. I continue to stand by the strategy that if SCT is on the table, waiting does not improve things and may make them worse