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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Chronic myeloid leukaemia can accelerate and then transform into an acute leukaemia called blast crisis. Tyrosine kinase inhibitors are given at full strength, combined with acute leukaemia chemotherapy in blast phase, to bring the disease back to chronic phase quickly enough for a donor stem cell transplant, the only treatment that cures it.
Accelerated phase is defined by 10 to 19 percent blasts in blood or marrow (WHO; the ELN and ICC use 15 to 29 percent and additional criteria), basophils of 20 percent or more, thrombocytopenia unrelated to treatment, or new clonal chromosomal abnormalities on top of the Philadelphia chromosome; the ICC 2022 classification folds most accelerated-phase features into high-risk chronic phase. Blast phase is 20 percent or more blasts (30 percent by ELN) or an extramedullary blast proliferation, and is myeloid in two thirds and lymphoid in a third. Additional mutations in ASXL1, RUNX1, IKZF1 and TP53 accumulate with progression, and resistance mutations in the BCR::ABL1 kinase domain are common.
Treatment aims to return the disease to a second chronic phase and consolidate with allogeneic transplant, the only curative treatment. In accelerated phase a second- or third-generation inhibitor at the higher dose, chosen by mutation testing (ponatinib for T315I, asciminib in trials), can restore a chronic phase lasting years, and transplant is reserved for poor responders. In blast phase the inhibitor is combined with acute leukaemia induction: 7+3-type chemotherapy for myeloid blast phase, or ALL-type regimens, or blinatumomab and inotuzumab for lymphoid blast phase, where dasatinib and ponatinib are favoured for their activity in the central nervous system. Patients who reach transplant in a second chronic phase have long-term survival in a substantial minority; those transplanted in overt blast phase rarely do.
| Setting | Approach | Guideline |
|---|---|---|
| Accelerated phase | Second- or third-generation tyrosine kinase inhibitor at full dose guided by mutation testing (dasatinib, nilotinib, bosutinib, ponatinib for T315I, olverembatinib where approved); allogeneic transplant if response is poor or clonal evolution progresses. | not mapped |
| Myeloid blast phase | Tyrosine kinase inhibitor (ponatinib or dasatinib) with 7+3-type or hypomethylating agent and venetoclax induction, then allogeneic transplant in second chronic phase. | not mapped |
| Lymphoid blast phase | Dasatinib or ponatinib with ALL-type chemotherapy or with blinatumomab, central nervous system prophylaxis, then allogeneic transplant. | not mapped |
| Consolidation | Allogeneic stem cell transplant for every eligible patient in second chronic phase, with tyrosine kinase inhibitor maintenance after transplant. | not mapped |