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Managing myeloid blast crisis

2 years 1 month ago #1799 by
Dear colleagues, we appreciate your opinion on this challenging case.
23M diagnosed with CP CML in 2014 (WCC >600 and 4% blasts in PB). Normal karyotype with no ACA. On dasatinib 100mg he reached bcr-abl 0.52% by 6 months but never <0.16% with poor compliance.
After a few years of complete non-compliance, he presented in blast crisis with >80% myeloblasts in BM aspirate. BCR-ABL 740% IS. Cytogenetics t(9;22;10;11). Myeloid NGS identified WT1 mutation. TKD mutation negative.
He received 7 days of cytarabine, 5 days of idarubicin and was transferred to Australia. D25 BM aspirate showed 25% myeloblasts (BCR-ABL 42%). He proceeded to FLAG-IDA salvage along with introducing ponatinib 45mg daily. He tolerated this well besides episodes of febrile neutropenia. Hypocellular D35 aspirate and trephine both showed marked dysplasia but <5% blasts, with BCR-ABL now at 16%. Incomplete recovery Neuts 0.9, Plt 45. Numerous infected teeth need removal so he remains on Ponatinib alone with plans for repeat BMA in a few weeks.
What next?
Obtaining an available overseas cord for alloSCT will take time.
Post dental recovery do you agree with another FLAG-IDA?
What about adding asciminib to ponatinib? We remain nervous about the potential for a TKD mutation.
  • Jorge Cortes
  • Jorge Cortes's Avatar
2 years 1 month ago - 2 years 1 month ago #1800 by Jorge Cortes
Replied by Jorge Cortes on topic Managing myeloid blast crisis
I agree with the plan to do a consolidation/2nd cycle FLAG-Ida + ponatinib. I would not add asciminib to ponatinib. The benefit is uncertain, there is not data on proper dosing of the combination, much less with chemotherapy also. I would start the next cycle as soon as possible and try to get to a SCT as soon as a donor is identified.
Last edit: 2 years 1 month ago by arlene.
  • Jeff Lipton
  • Jeff Lipton's Avatar
2 years 1 month ago - 2 years 1 month ago #1801 by Jeff Lipton
Replied by Jeff Lipton on topic Managing myeloid blast crisis
I agree completely with Jorge. An urgent allograft is necessary if CP2 or even AP can be obtained. I notice that the only comment is about a cord blood. What about a haplo graft? Without a transplant, the response if any, is only transient. Would reduce the ponatinib dose to 30 during the chemo part (due to interaction with some of the drugs used during induction) and then increase immediately after to 45. Assuming the patient gets to a transplant, would withdraw immunosuppression in the absence of GVHD promptly, starting around day 45 and finishing within a couple of weeks. Would continue probably lifelong ponatinib post allograft starting around day 60 if off immunosuppression – first year at 45 and thereafter at 30 (due to long term chronic toxicity at 45), assuming toleration.
Biggest potential problem here is compliance. My experience in similar cases, is that patients who do not take TKIs are very often non-compliant in allograft related meds. Good luck.
Last edit: 2 years 1 month ago by arlene.
  • Judith Trotman
  • Judith Trotman's Avatar
2 years 1 month ago - 2 years 1 month ago #1802 by Judith Trotman
Replied by Judith Trotman on topic Managing myeloid blast crisis
Many thanks both!
We hope to start 2nd cycle FLAG IDA as soon as mouth healed following 10 extractions this week. He has a haplo donor (father who could be brought from OS) and I will pass your feedback on to the allo transplant team. I have kept the Ponatinb at 45 mg and used amphotericin 3x/week as fungal prophylaxis rather than azole. Is the rationale for 30mg related to cytopenia risk? Agree with sobering comments re. compliance. Best regards.
Last edit: 2 years 1 month ago by arlene.
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