{"entity":{"id":"cml-advanced-phase","kind":"cancer","name":"Chronic myeloid leukaemia, accelerated and blast phase","aka":["CML-AP","CML-BP","Blast crisis","Advanced-phase CML","Accelerated-phase CML"],"tldr":"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.","summary":"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.\n\nTreatment 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.\n\nProgression is now rare enough that trials are small and outcomes come from registries (the CML-IV and ELN blast phase studies). Prevention through early achievement of molecular milestones and prompt switching on failure is the practical strategy, and the biology of the leukaemic stem cell that acquires these extra hits is the research question.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia"},{"label":"NCCN Guidelines: Chronic Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":["allogeneic-hsct","kinase-inhibitors","cytogenetics-fish"],"targets":["bcr-abl"],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-abl1-signalling"],"terms":["blasts","philadelphia-chromosome","allogeneic-transplant","tki-term","resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Fewer than one in twenty patients now present in accelerated or blast phase, and progression from chronic phase on treatment has fallen to around one percent a year; blast phase remains the most dangerous form of the disease, with survival historically under a year.","subtypes":["Accelerated phase CML (10 to 19 percent blasts, basophilia or clonal evolution)","Myeloid blast phase CML","Lymphoid blast phase CML (dasatinib or ponatinib with ALL-type therapy)","De novo blast phase at presentation","Extramedullary blast phase (myeloid sarcoma)","Second chronic phase after treatment of blast phase (transplant candidate)"],"biomarkers":["Blast percentage in blood and marrow","Basophil percentage and platelet count","Additional chromosomal abnormalities (clonal evolution)","BCR::ABL1 kinase domain mutations including T315I","Blast lineage by flow cytometry (myeloid or lymphoid)","ASXL1, RUNX1, IKZF1 and TP53 mutations","Donor availability"],"standardOfCare":[{"setting":"Accelerated phase","approach":"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.","refs":["dasatinib","nilotinib","bosutinib","ponatinib","olverembatinib","asciminib","nct04233346","nct06514534","allogeneic-hsct"],"guideline":{"version":"NCCN Guidelines: Chronic Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427"}},{"setting":"Myeloid blast phase","approach":"Tyrosine kinase inhibitor (ponatinib or dasatinib) with 7+3-type or hypomethylating agent and venetoclax induction, then allogeneic transplant in second chronic phase.","refs":["ponatinib","dasatinib","cytarabine-7-3","cytarabine","azacitidine","venetoclax","allogeneic-hsct"],"guideline":{"version":"NCCN Guidelines: Chronic Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427"}},{"setting":"Lymphoid blast phase","approach":"Dasatinib or ponatinib with ALL-type chemotherapy or with blinatumomab, central nervous system prophylaxis, then allogeneic transplant.","refs":["dasatinib","ponatinib","blinatumomab","cyclophosphamide","allogeneic-hsct","tki-plus-blinatumomab-ph-all"],"guideline":{"version":"NCCN Guidelines: Chronic Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427"}},{"setting":"Consolidation","approach":"Allogeneic stem cell transplant for every eligible patient in second chronic phase, with tyrosine kinase inhibitor maintenance after transplant.","refs":["allogeneic-hsct","allogeneic-transplant","conditioning-regimen"],"guideline":{"version":"NCCN Guidelines: Chronic Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427"}}],"stateOfArt":["Tyrosine kinase inhibitors have made progression rare: around one percent of chronic-phase patients a year.","Blast phase is treated as an acute leukaemia with an inhibitor added, and cured only by transplant in a second chronic phase.","Third-generation inhibitors cover T315I in advanced phase, and chemotherapy-free inhibitor-plus-antibody regimens are being borrowed from Philadelphia-positive ALL."],"history":[{"year":1980,"title":"Blast crisis defined; median survival months with chemotherapy","refs":["blasts"]},{"year":2001,"title":"Imatinib produces responses in blast phase, though short-lived","refs":["imatinib"]},{"year":2012,"title":"Ponatinib approved for advanced phase including T315I","refs":["ponatinib"]},{"year":2021,"title":"Olverembatinib approved in China for T315I chronic and accelerated phase","refs":["olverembatinib"]},{"year":2022,"title":"ICC and WHO redefine accelerated and blast phase thresholds","refs":[]}],"pipeline":["ponatinib","asciminib","olverembatinib","blinatumomab","nct04233346","nct06514534","allogeneic-hsct"],"openProblems":["Blast phase remains largely fatal without transplant, and few patients reach it in remission.","Trials are tiny because progression has become rare.","The mutations that drive progression are known but not targetable."],"parent":"cml"},"route":"/cancers/cml-advanced-phase/","neighbours":{"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/"}],"pathway":[{"id":"bcr-abl1-signalling","kind":"pathway","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/pathways/bcr-abl1-signalling/"}],"term":[{"id":"allogeneic-transplant","kind":"term","name":"Allogeneic stem cell transplant (allo-SCT)","route":"/terms/allogeneic-transplant/"},{"id":"blasts","kind":"term","name":"Blasts (leukaemic blast cells)","route":"/terms/blasts/"},{"id":"conditioning-regimen","kind":"term","name":"Conditioning regimen (myeloablative, reduced-intensity)","route":"/terms/conditioning-regimen/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"philadelphia-chromosome","kind":"term","name":"Philadelphia chromosome (Ph+, BCR::ABL1)","route":"/terms/philadelphia-chromosome/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"}],"drug":[{"id":"asciminib","kind":"drug","name":"Asciminib","route":"/drugs/asciminib/"},{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/"},{"id":"bosutinib","kind":"drug","name":"Bosutinib","route":"/drugs/bosutinib/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"cytarabine","kind":"drug","name":"Cytarabine","route":"/drugs/cytarabine/"},{"id":"cytarabine-7-3","kind":"drug","name":"Cytarabine + anthracycline ('7+3')","route":"/drugs/cytarabine-7-3/"},{"id":"dasatinib","kind":"drug","name":"Dasatinib","route":"/drugs/dasatinib/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"nilotinib","kind":"drug","name":"Nilotinib","route":"/drugs/nilotinib/"},{"id":"olverembatinib","kind":"drug","name":"Olverembatinib","route":"/drugs/olverembatinib/"},{"id":"ponatinib","kind":"drug","name":"Ponatinib","route":"/drugs/ponatinib/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"trial":[{"id":"nct06514534","kind":"trial","name":"Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.","route":"/trials/nct06514534/"},{"id":"nct04233346","kind":"trial","name":"The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs or With T315I Mutation","route":"/trials/nct04233346/"}],"pairing":[{"id":"tki-plus-blinatumomab-ph-all","kind":"pairing","name":"BCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL)","route":"/pairings/tki-plus-blinatumomab-ph-all/"}],"cancer":[{"id":"cml","kind":"cancer","name":"Chronic myeloid leukaemia (CML)","route":"/cancers/cml/"}]}}