# Chronic myeloid leukaemia, accelerated and blast phase

Source: https://onco.cc/cancers/cml-advanced-phase/  
OnCo record `cml-advanced-phase` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

Progression 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: CML-AP; CML-BP; Blast crisis; Advanced-phase CML; Accelerated-phase CML
- Tags: subtype-page
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/cml-advanced-phase/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/cml-advanced-phase/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/cml-advanced-phase/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/cml-advanced-phase/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/cml-advanced-phase/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/cml-advanced-phase/#evidence [4 trials, 4 key papers, 5 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/cml-advanced-phase/#science [8 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/cml-advanced-phase/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/cml-advanced-phase/#living-with-it [17 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/cml-advanced-phase/coming/ [13 medicines, 4 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/cml-advanced-phase/data/ [57 connected records]

## Standard of care

- 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. ([Dasatinib](https://onco.cc/drugs/dasatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Bosutinib](https://onco.cc/drugs/bosutinib/), [Ponatinib](https://onco.cc/drugs/ponatinib/), [Olverembatinib](https://onco.cc/drugs/olverembatinib/), [Asciminib](https://onco.cc/drugs/asciminib/), [The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs or With T315I Mutation](https://onco.cc/trials/nct04233346/), [Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.](https://onco.cc/trials/nct06514534/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))
- 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. ([Ponatinib](https://onco.cc/drugs/ponatinib/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Cytarabine + anthracycline ('7+3')](https://onco.cc/drugs/cytarabine-7-3/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))
- Lymphoid blast phase: Dasatinib or ponatinib with ALL-type chemotherapy or with blinatumomab, central nervous system prophylaxis, then allogeneic transplant. ([Dasatinib](https://onco.cc/drugs/dasatinib/), [Ponatinib](https://onco.cc/drugs/ponatinib/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [BCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL)](https://onco.cc/pairings/tki-plus-blinatumomab-ph-all/))
- Consolidation: Allogeneic stem cell transplant for every eligible patient in second chronic phase, with tyrosine kinase inhibitor maintenance after transplant. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Allogeneic stem cell transplant (allo-SCT)](https://onco.cc/terms/allogeneic-transplant/), [Conditioning regimen (myeloablative, reduced-intensity)](https://onco.cc/terms/conditioning-regimen/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia
- Wikipedia: https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia
- NCCN Guidelines: Chronic Myeloid Leukemia: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427

## Connected records

- cancers: [Chronic myeloid leukaemia (CML)](https://onco.cc/cancers/cml/), [Chronic myeloid leukaemia, chronic phase](https://onco.cc/cancers/cml-chronic-phase/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ABL1](https://onco.cc/targets/abl1/), [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/), [STAT5 (STAT5A, STAT5B)](https://onco.cc/targets/stat5/)
- pathways: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/pathways/bcr-abl1-signalling/)
- terms: [Allogeneic stem cell transplant (allo-SCT)](https://onco.cc/terms/allogeneic-transplant/), [BCR::ABL1 kinase domain mutations (T315I and others)](https://onco.cc/terms/abl1-kinase-domain-mutations/), [Blasts (leukaemic blast cells)](https://onco.cc/terms/blasts/), [Conditioning regimen (myeloablative, reduced-intensity)](https://onco.cc/terms/conditioning-regimen/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Philadelphia chromosome (Ph+, BCR::ABL1)](https://onco.cc/terms/philadelphia-chromosome/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- key papers: [European LeukemiaNet 2020 recommendations for treating chronic myeloid leukaemia](https://onco.cc/key-papers/paper-eln-2020-cml-hochhaus-leukemia-2020/), [IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia](https://onco.cc/key-papers/paper-iris-imatinib-nejm-2003/), [PACE: ponatinib in Philadelphia chromosome-positive leukaemias resistant to earlier tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-pace-ponatinib-nejm-2013/), [WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms](https://onco.cc/key-papers/paper-who-2022-myeloid-khoury-leukemia-2022/)
- drugs: [Asciminib](https://onco.cc/drugs/asciminib/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Bosutinib](https://onco.cc/drugs/bosutinib/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Cytarabine + anthracycline ('7+3')](https://onco.cc/drugs/cytarabine-7-3/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Olverembatinib](https://onco.cc/drugs/olverembatinib/), [Ponatinib](https://onco.cc/drugs/ponatinib/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- trials: [Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.](https://onco.cc/trials/nct06514534/), [Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients](https://onco.cc/trials/nct05433532/), [TGRX-678 Chinese Phase II in Chronic Myelogenous Leukemia (CML) Patients](https://onco.cc/trials/nct06453902/), [The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs or With T315I Mutation](https://onco.cc/trials/nct04233346/)
- pairings: [BCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL)](https://onco.cc/pairings/tki-plus-blinatumomab-ph-all/)
- biomarkers: [BCR::ABL1 T315I](https://onco.cc/biomarkers/bcr-abl1-t315i/), [BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)](https://onco.cc/biomarkers/bcr-abl1-transcript/)

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JSON: https://onco.cc/api/v1/entities/cml-advanced-phase.json